The DOI matches its Crossref record; 268 of the 268 references it cites were found in a registry or an index; none of the 253 sources its claims cite is checked for support yet.
Principles of interleukin (IL)-6-type cytokine signalling and its regulation
Open accessAbstract
The IL (interleukin)-6-type cytokines IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor, cardiotrophin-1 and cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the acute-phase response to injury and infection. Besides their functions in inflammation and the immune response, these cytokines play also a crucial role in haematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of IL-6-type cytokine signalling contributes to the onset and maintenance of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, osteoporosis, multiple sclerosis and various types of cancer (e.g. multiple myeloma and prostate cancer). IL-6-type cytokines exert their action via the signal transducers gp (glycoprotein) 130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) cascades. This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction. Emphasis is put on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins. Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review summarizes IL-6-type cytokine signalling through gp130, LIFR and OSMR, covering JAK/STAT and MAPK activation and the mechanisms that terminate or modulate these pathways. It emphasizes negative regulation by tyrosine phosphatases, SOCS feedback inhibitors and PIAS proteins, as well as cross-talk with other signalling cascades.
Key findings
- IL-6-type cytokines (IL-6, IL-11, LIF, OSM, CNTF, CT-1 and CLC) signal via gp130 homodimers or gp130–LIFR/OSMR heterodimers; all potently activate STAT3 and, to a lesser extent, STAT1 through gp130, while OSMR is the most potent activator of STAT5.
- Receptor activation requires more than simple dimerization: efficient gp130 activation by monoclonal antibodies required two distinct antibodies, with the minimal requirement being one intact antibody plus the Fab of a second; insertion of one to four alanines into the gp130 membrane-proximal intracellular region gave full activation only with wild-type and the +3A mutant, interpreted as an approx. 110° twist per alanine and approx. 330° for three.
- JAK1 is essential for IL-6 signalling; gp130, LIFR and OSMR bind JAK1, JAK2 and TYK2. JAK1 mobility is approx. 100-fold lower than that of a typical cytoplasmic protein, and gp130 residues including box1 prolines and Trp666 are critical for JAK binding, while W652A abrogates JAK1 activation without affecting JAK1 association.
- Signal termination involves SHP2 and SOCS3 at gp130 pTyr759, with SOCS3 binding gp130 peptides with slightly higher affinity than SHP2; SOCS1 and SOCS3 inhibit JAKs, PIAS1 inhibits STAT1 and PIAS3 inhibits STAT3. Reported half-lives include SOCS1 1.5 h, SOCS2 1 h, SOCS3 1.6 h, IL-6Rα 2–3 h, gp130 2.5 h, JAK1 3.2 h, JAK2 1.9 h, TYK2 2 h, STAT3α 8.5 h, STAT3β 4.5 h, STAT1 16 h and SHP-2 18–20 h.
Methods
- Narrative review of molecular mechanisms of IL-6-type cytokine signal transduction, focusing on advances made during the previous 5 years in receptor activation, JAK–receptor interactions, STAT activation, signal modulation and cross-talk.
- Synthesizes structural, mutagenesis, biochemical and in vivo findings from the literature; no primary experimental dataset is presented, and the text includes models and a table of half-lives drawn from cited studies.
Limitations
- The authors state that key structural data are still missing, including the structure and conformational states of the cytoplasmic parts of cytokine receptors, and that three-dimensional structures of JAKs and SOCS proteins would be extremely valuable.
- The authors state that mathematical models of this complexity suffer from a lack of sufficient quantitative experimental data, and that cross-talk and biological outcomes depend on cell type and differentiation state.
- Evident from the text: as a narrative review, it does not use a systematic search or meta-analysis, and it includes unpublished work/personal communications and unresolved conflicting findings, such as JNK versus p38 involvement in STAT3 Ser727 phosphorylation and the positive versus negative regulatory functions reported for STAT3β.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
172 Sources not found · 17 Own interpretation · 16 No basis given · 7 Not checked yet · 2 Own result
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Human OSM has the exceptional capability to recruit two different receptor complexes.It forms both LIFR-gp130 and OSMR-gp130 heterodimers.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“LIF and OSM directly engage their signalling receptor subunits without requirement for additional α-receptor subunits (Figure 2) [4,6].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [6]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“Soluble forms of cytokine receptors in vivo are formed either by limited proteolysis (shedding) of membrane-bound receptors or by translation from an alternatively spliced mRNA [4].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“It has been demonstrated that sIL-6Rα potentiates the antagonistic activity of sgp130.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [7]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“In contrast with IL-6, and presumably also IL-11, where all the helices are straight, the A helix of LIF, OSM and CNTF is kinked [17,18].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [17]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [18]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“The minimal requirement for receptor activation is one intact antibody and the Fab (fragment antigen binding) of the second antibody.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptors at work: let's do the twist
What the sources say
- Not matchedcites [39]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [40]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“It has been shown that these domains are necessary for coupling ligand binding and signal transduction, since deletion of these domains leads to signalling incompetent receptors [36,37].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptors at work: let's do the twist
What the sources say
- Not matchedcites [36]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [37]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“Thus in the homodimer two different binding epitopes of gp130 are involved in ligand recognition [23].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [23]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“The interaction sites predicted by mutagenesis studies have recently been confirmed by the X-ray structure of KSHV-IL-6 bound to a soluble gp130 fragment comprising the CBM and the Ig-like domain [24].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [24]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“In contrast with the α-receptors, the receptors that initiate signal transduction have three additional membrane-proximal FNIII domains [4].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
- Probably not a substantial claim. 16
- It may state two separate claims as one. 55
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This structural divergence might reflect differences in the mechanisms of receptor recruitment, since the straight cytokines signal via gp130 homodimers, whereas the kinked cytokines signal via LIFR-gp130 or OSMR-gp130 heterodimers.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Of these, JAK1 plays an essential role, because in cells lacking JAK1 IL-6 signal transduction is greatly impaired [51,52,134].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptor-JAK interaction: more than just a rendez-vous
What the sources say
- Not matchedcites [51]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [52]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [134]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“This finding has been interpreted in a way that the bivalent intact antibody enforces receptor dimerization and the monovalent Fab adjusts the conformation required for JAK activation and downstream signalling [40].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptors at work: let's do the twist
What the sources say
- Not matchedcites [40]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Some evidence has been provided that under certain circumstances gp130 and LIFR are degraded after internalization [30][31][32].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [30]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [31]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [32]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“While for gp130, the STATs were found to depend on a specific conformation in order to become phosphorylated, for the EpoR the receptor phosphorylation seems to be sensitive to changes in orientation.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptors at work: let's do the twist
What the sources say
- Not matchedcites [45]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [46]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“KSHV-IL-6 binds the gp130 homodimer in the absence of any α-receptor [16], but with lower affinity as compared with IL-6-IL-6Rα-gp130 ternary complexes.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [16]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Internalization of gp130 seems to be independent from ligand binding [28], and is modulated by phosphorylation at Ser 782 [29] which is located adjacent to the dileucine motif.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [28]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [29]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“ErbB2 forms a complex with gp130 in an IL-6-dependent manner in prostate carcinoma cells [35].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [35]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“In certain cell types, a localization of gp130 in plasma membrane microdomains, such as lipid rafts and caveolae, has been observed [9][10][11].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [9]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [10]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“After secretion of the CLC-CLF-1 or CLC-CNTFRα complexes, signalling is dependent on CNTFRα and occurs via gp130-LIFR heterodimers.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > INTRODUCTION
What the sources say
- Not matchedcites [12]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [13]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Constantinescu et al. [46] identified a hydrophobic motif in the EpoR membrane-proximal domain (Leu 253 , Ile 257 and Trp 258 ) which is conserved in many cytokine receptors and needs to be precisely orientated in order to promote signalling.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptors at work: let's do the twist
What the sources say
- Not matchedcites [46]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“PKCδ enhances the association of STAT3 with the receptor, which possibly involves the phosphorylation of Thr 890 of gp130 [67].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptor-JAK interaction: more than just a rendez-vous
What the sources say
- Not matchedcites [67]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“All IL-6-type cytokines potently activate STAT3, and to a minor extent STAT1 through their common receptor subunit gp130 [4].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Another face of JAKs: determination of the receptor's fate
What the sources say
- Not matchedcites [4]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“The Cterminal tyrosine kinase domain is preceded by a pseudokinase domain, which itself is devoid of catalytic activity, but regulates the activity of the kinase domain [3].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptor-JAK interaction: more than just a rendez-vous
What the sources say
- Not matchedcites [3]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“In the cases of LIFR and OSMR, STAT3 and STAT1, as well as STAT5, activation has been observed, with OSMR being the most potent activator of STAT5 [56].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Another face of JAKs: determination of the receptor's fate
What the sources say
- Not matchedcites [56]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“These results were confirmed by Chung et al. [105], who also observed that IL-6-induced STAT3 activation is MAPK independent, but sensitive to H7.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Serine phosphorylation
What the sources say
- Not matchedcites [105]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Cdk9 (cyclin-dependent kinase 9) was also found to bind to gp130, and the association increased upon IL-6 stimulation of HEK 293 cells over-expressing gp130 and Cdk9 [66].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptor-JAK interaction: more than just a rendez-vous
What the sources say
- Not matchedcites [66]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Deletion of these amino acids reduces IL-6-induced Hck kinase activity, ERK (extracellular-regulated kinase) activation, dephosphorylation of Pyk2 and proliferation of transfected pro-B Ba/F3 cells [65].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptor-JAK interaction: more than just a rendez-vous
What the sources say
- Not matchedcites [65]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“A conformational change in the SH2 domain may account for this dual specificity [91].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Another face of JAKs: determination of the receptor's fate
What the sources say
- Not matchedcites [91]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“The recruitment of STATs to the activated receptors has been shown to be mediated by their SH2 domain and requires the phosphorylation of receptor tyrosine motifs [74,[81][82][83].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Another face of JAKs: determination of the receptor's fate
What the sources say
- Not matchedcites [74,[81][82][83]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“substitution of Trp 652 with alanine (W652A) within the box1 region has no effect on JAK1 association but abrogates JAK1 activation.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptor-JAK interaction: more than just a rendez-vous
What the sources say
- Not matchedcites [55]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Mutations with similar consequences (no JAK activation in spite of JAK association) have been described for the EpoR [59], indicating that cytokine receptors in general contribute to the JAK-activation process.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptor-JAK interaction: more than just a rendez-vous
What the sources say
- Not matchedcites [59]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“human fibrosarcoma cells lacking JAK1 express less OSMR at their surface compared with the parental cells, but transient transfection of JAK1 can again increase the amount of surface-expressed receptors [49].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Another face of JAKs: determination of the receptor's fate
What the sources say
- Not matchedcites [49]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Box2 of gp130, a sequence dominated by hydrophobic amino acids followed by charged ones, contributes to JAK binding, presumably by increasing the affinity; a gp130 construct lacking box2 coprecipitates with JAK1 only when the kinase is over-expressed [55].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Receptor-JAK interaction: more than just a rendez-vous
What the sources say
- Not matchedcites [55]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“This leads to the formation of active STAT dimers, also shown to be mediated by their SH2 domains [90].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Another face of JAKs: determination of the receptor's fate
What the sources say
- Not matchedcites [90]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In response to IL-6, Gab1 is tyrosine phosphorylated and interacts subsequently with SHP2 and PI3K.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Activation of MAPK cascades: one tyrosine to make things more complicated
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent study [112] on STAT3 activation in response to EGF (epidermal growth factor) suggests that receptor-mediated endocytosis is required for shuttling of STAT3 from the plasma membrane to the perinuclear region.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT nuclear translocation: not a one way ticket
What the sources say
- Not matchedcites [112]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“In the DNA-binding domain of STAT1, initially an NES was postulated that comprises residues 399-410 [108].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT nuclear translocation: not a one way ticket
What the sources say
- Not matchedcites [108]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“Compared with the unmethylated protein, methylated STAT1 has a higher tendency to associate with DNA, since its interaction with PIAS (protein inhibitor of activated STATs) 1 (see the subsection below entitled 'PIAS -more than inhibitors of activated STATs?') seems to be weaker [106].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Methylation of STATs
What the sources say
- Not matchedcites [106]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“The family of IL-6-type cytokines not only activates ERK1/2, a MAPK known for cellular processes that maintain cell survival, but also the stress-activated members of the MAPK family: p38 and JNK [140-142] (Figure 6).”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Activation of MAPK cascades: one tyrosine to make things more complicated
What the sources say
- Not matchedcites [140]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [141]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [142]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Sensitivity to leptomycin suggests that nuclear export of STAT1 involves the nuclear export receptor CRM-1 that also acts in a Randependent manner [108,109].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT nuclear translocation: not a one way ticket
What the sources say
- Not matchedcites [108]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [109]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“However, from an earlier study [113], it was concluded that nuclear translocation of STAT1 in response to IFNγ does not require cytoskeletal structures, such as actin filaments or microtubules.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT nuclear translocation: not a one way ticket
What the sources say
- Not matchedcites [113]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“According to the current view of the SHP2-dependent activation of MAPKs adopted from EGF and PDGF (platelet-derived growth factor) signal transduction, SHP2 links the Grb2-SOS (growthfactor-receptor-bound protein/Son of Sevenless) complex and/or Gab1 (Grb2-associated binder-1) to gp130 [127,129,130].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Activation of MAPK cascades: one tyrosine to make things more complicated
What the sources say
- Not matchedcites [127]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [129]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [130]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“In response to IL-2, Epo, EGF, and PDGF, SOCS3 (suppressor of cytokine signalling 3) becomes tyrosine phosphorylated, and subsequently binds and inactivates Ras/GTPase-activating protein.This results in the inhibition of the GTPase activity of Ras, leading to a sustained Ras/GTP and MAPK activity [139].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Activation of MAPK cascades: one tyrosine to make things more complicated
What the sources say
- Not matchedcites [139]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“SHP2 is rapidly recruited to tyrosine-phosphorylated gp130 and becomes also phosphorylated in a JAK1-dependent manner [131].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Activation of MAPK cascades: one tyrosine to make things more complicated
What the sources say
- Not matchedcites [131]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Dimerization of IL-6-type cytokine receptors does not only lead to activation of the JAK/STAT-signalling pathway, but also to the induction of the MAPK cascade.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Activation of MAPK cascades: one tyrosine to make things more complicated
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Furthermore, nuclear accumulation of constitutively active STAT proteins is independent from endocytosis, because in these cases the STATs are not recruited to any plasma membrane receptor [110,114].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT nuclear translocation: not a one way ticket
What the sources say
- Not matchedcites [110]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [114]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“PIAS1 inhibits STAT1 signalling [179], but conversely enhances the transcriptional activity of nuclear hormone receptors [180].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > PIAS -more than inhibitors of activated STATs?
What the sources say
- Not matchedcites [179]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [180]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Whereas SHP2 modulates the amount and amplitude of STAT3 activity [131,158], PTPεC affects the kinetics of the onset of STAT3 activation [169].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Protein tyrosine phosphatases (PTPs): what goes up must come down
What the sources say
- Not matchedcites [131]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [158]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [169]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“It should be noted, however, that PI3K activation upon IL-6 treatment is observed in a cell-type specific manner; e.g.no significant Akt activation could be observed in IL-6treated HepG2 hepatoma cells [149].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Activation of the PI3K cascade: the lipid connection
What the sources say
- Not matchedcites [149]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This enzyme modifies certain phosphatidylinositides, so that the serine/threonine kinase protein kinase B/Akt is recruited to the plasma membrane, where it becomes activated through phosphorylation by PDK1 (phosphoinositide-dependent kinase-1).”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Activation of the PI3K cascade: the lipid connection
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Early results suggested the presence of a nuclear phosphatase which counteracts IFNγ -activated STAT1 and contributes to its nuclear export [121,173].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Protein tyrosine phosphatases (PTPs): what goes up must come down
What the sources say
- Not matchedcites [121]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [173]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Interaction of SHP2 with JAK1, JAK2 and TYK2, and phosphorylation of SHP2 by JAK1 and JAK2, have at least been shown to occur in vitro [131,162].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Protein tyrosine phosphatases (PTPs): what goes up must come down
What the sources say
- Not matchedcites [131]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [162]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“IL-6-induced activation of the PI3K/Akt pathway is involved in protection against apoptosis, as well as in enhanced proliferation of multiple myeloma cells [145][146][147].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Activation of the PI3K cascade: the lipid connection
What the sources say
- Not matchedcites [145]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [146]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [147]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“The cytoplasmic variant of PTPε, PTPεC, is expressed in haematopoietic cells and has been shown to selectively inhibit IL-6-induced gp130, JAK and STAT activation [168].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Protein tyrosine phosphatases (PTPs): what goes up must come down
What the sources say
- Not matchedcites [168]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, the IL-6induced activation of the MAPK cascade is impaired by mutation of Tyr 759 within gp130, indicating that SHP2, as an adaptor, has a positive function on the activation of the MAPK cascade (as shown in Figure 1).”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Protein tyrosine phosphatases (PTPs): what goes up must come down
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The family of PIAS comprises five mammalian members: PIAS1, PIAS3, PIASxα, PIASxβ, and PIASy.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > PIAS -more than inhibitors of activated STATs?
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus methylation not only supports STAT activity (by preventing PIAS association), but also promotes its inactivation by dephosphorylation.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Protein tyrosine phosphatases (PTPs): what goes up must come down
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Experiments in vivo underscore the in vitro findings in demonstrating that mice expressing gp130 lacking Tyr 759 display splenomegaly, lymphadenopathy and an enhanced acute-phase reaction [161].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Protein tyrosine phosphatases (PTPs): what goes up must come down
What the sources say
- Not matchedcites [161]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These differences suggest that signalling components requiring posttranslational modifications for their activation are long-lived, whereas the activity of short-lived proteins is regulated mainly at the transcriptional level.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Half-lives of signalling components: party as long as you live
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Whereas the feedback inhibitors SOCS1, SOCS2 and SOCS3 are very short-lived, STAT1, STAT3α and SHP2 have slow turnover rates.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > Half-lives of signalling components: party as long as you live
What the sources say
- Not matchedcites [222]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [223]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The eight members of this family (CIS and SOCS1-SOCS7) contain a central SH2 domain, as well as a C-terminal domain called a SOCS box (Figure 4).”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > The SOCS family of feedback inhibitors: natural born terminators
plainn = 8- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“For gp130, SOCS3 has been found to bind to the phosphotyrosine motif 759 [197,198], which is also the binding site for SHP2.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > The SOCS family of feedback inhibitors: natural born terminators
What the sources say
- Not matchedcites [197]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [198]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Phosphorylation occurs at two tyrosine residues (Tyr 204 and Tyr 221 ) within the SOCS box and phosphorylation of Tyr 221 recruits p120 RasGAP leading to sustained ERK activation [139].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > The SOCS family of feedback inhibitors: natural born terminators
What the sources say
- Not matchedcites [139]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Other reports, however, suggest that elongin C binding can stabilize SOCS1 and that the disruption of the interaction leads to proteasomal degradation of SOCS1 [206,215].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > The SOCS family of feedback inhibitors: natural born terminators
What the sources say
- Not matchedcites [206]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [215]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Expression of SOCS proteins was found to be rapidly up-regulated by IL-6 (CIS, SOCS1, SOCS2 and SOCS3), LIF (CIS, SOCS1, SOCS2 and SOCS3), IL-11 (SOCS3) and OSM (CIS, SOCS1 and SOCS3) [32,190,192,193].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > The SOCS family of feedback inhibitors: natural born terminators
What the sources say
- Not matchedcites [32]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [190]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [192]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As SOCS proteins are induced via the JAK/STAT pathway and subsequently inhibit STAT-mediated signal transduction, they are acting as classical feedback inhibitors.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > The SOCS family of feedback inhibitors: natural born terminators
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These phosphotyrosine residues may be part of an activated receptor or the tyrosine-phosphorylated C-terminal tail of SHP2 (from [156]).”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > PERSPECTIVES
What the sources say
- Not matchedcites [156]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“FKHR specifically enhanced the activity of STAT3-dependent promoters, such as the α 2 M promoter, but not that of a STAT5-responsive promoter.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT action within the transcriptosome: where transcription factors gather
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Other signalling pathways have been shown to induce stabilization of cytokine mRNAs as well: the JNK pathway induces stabilization of the short-lived IL-2 mRNA [219], and PI3K activation induces stabilization of IL-3 mRNA [220].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > PERSPECTIVES
What the sources say
- Not matchedcites [219]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [220]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“PI3K activation induces stabilization of IL-3 mRNA [220]”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > PERSPECTIVES
What the sources say
- Not matchedcites [220]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
In the paper
“The nuclear receptor co-repressor SMRT (silencing mediator of retinoic and thyroid hormone receptors) is a potential binding partner for STAT5 and represses STAT5-dependent transcription [255].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT action within the transcriptosome: where transcription factors gather
What the sources say
- Not matchedcites [255]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Furthermore, FKHR and STAT3 can be co-immunoprecipitated and co-localize in the nucleus of IL-6-treated HepG2 cells [149].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT action within the transcriptosome: where transcription factors gather
What the sources say
- Not matchedcites [149]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“the JNK pathway induces stabilization of the short-lived IL-2 mRNA [219]”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > PERSPECTIVES
What the sources say
- Not matchedcites [219]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Not matched
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, an EZI mutant predominantly localized in the cytoplasm inhibited nuclear localization of STAT3, as well as STAT3-mediated transactivation.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT action within the transcriptosome: where transcription factors gather
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Interestingly, Nmi itself is induced by IL-2 and IFNγ , indicating a positive feedback loop within this signal transduction.”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT action within the transcriptosome: where transcription factors gather
What the sources say
- Not matchedcites [253]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“This interaction is further modulated by Nmi (N-Myc interactor) which augments CBP recruitment to STAT1 and STAT5, and potentiates IL-2 and IFNγ signalling [253].”
§ Principles of interleukin (IL)-6-type cytokine signalling and its regulation 1 > STAT action within the transcriptosome: where transcription factors gather
What the sources say
- Not matchedcites [253]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The authors state this as an assumption.
The membrane-proximal FNIII domains bridge the ~9 nm distance between the CBM C-termini so that the cytoplasmic parts are close enough to become activated by associated JAKs.
“The membrane-proximal FNIII domains might bridge this distance so that the cytoplasmic parts are in close enough proximity to become activated by the associated JAKs (Figure 5).This assumption is supported by a recent study on the role of the gp130 FNIII domains for heterodimerization with the LIFR [38].”
The paper relies on this without support.
gp130 is ubiquitously expressed.
“Although gp130 is ubiquitously expressed, the number of cells that respond to a certain IL-6-type cytokine is limited, since the expression of the other receptor subunits, especially of the α-receptors, is more restricted and tightly regulated.”
The paper relies on this without support.
IL-6-type cytokines form a subfamily of helix bundle cytokines.
“IL-6-type cytokines form a subfamily of the helix bundle cytokines.”
The paper relies on this without support.
All IL-6-type cytokines comprise four long α-helices A-D arranged in an up-up-down-down topology.
“All IL-6-type cytokines comprise four long α-helices termed A, B, C and D, which are arranged in a way that leads to an up-up-down-down topology (Figure 3).”
The paper relies on this without support.
Each receptor contains at least one cytokine-binding module (CBM) comprising two FNIII domains.
“Each receptor contains at least one cytokine-binding module (CBM) that comprises two FNIII-domains.”
The paper relies on this without support.
JAKs bind to the membrane-proximal region of cytokine receptors, which contains conserved box1 and box2 motifs.
“JAKs bind to the membrane-proximal region of cytokine receptors, which contains conserved so-called box1 and box2 motifs.”
The paper relies on this without support.
The N-terminal region of JAKs comprises a FERM domain crucial for receptor association.
“The N-terminal region of JAKs comprises a FERM (fourpoint-one, ezrin, radixin and moesin) domain which is crucial for receptor association.”
The paper relies on this without support.
The STAT family encompasses seven mammalian members.
“The STAT family of transcription factors encompasses seven mammalian members, designated STAT1, -2, -3, -4, -5a, -5b and -6.”
The paper relies on this without support.
In response to IL-6 stimulation, cytoplasmic STAT3 rapidly accumulates in the nucleus.
“In response to IL-6 stimulation, cytoplasmic STAT3 rapidly accumulates in the nucleus.”
The paper relies on this without support.
Nuclear accumulation is triggered by STAT dimerization in response to tyrosine phosphorylation.
“Nuclear accumulation is triggered by STAT dimerization in response to tyrosine phosphorylation.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“IL-6Rα expression is normally associated with hepatocytes and leukocytes but has also been described in cancer cells, including PDAC.”
From Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells (2024) · cites this paper as [40]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The cytokine IL-6 triggers multiple downstream responses, including metabolic regulation.”
From Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells (2024) · cites this paper as [40]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“IL-6, which was discovered in 1986 (27), is a pleiotropic cytokine involved not only in immune responses but also in inflammation, hematopoiesis, bone metabolism, embryonic development and other fundamental processes (1, 21, 28–32).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [30]
Experimental — accuracy not yet measured
Citations
Cites
STATs: transcriptional control and biological impact
Levy, D. E., & Darnell, J. E. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm909 · Cited by 3,201
Bromberg, J. F., Wrzeszczynska, M. H., Devgan, G., Zhao, Y., Pestell, R. G., Albanese, C., & Darnell, J. E. (1999) · Cell · doi:10.1016/s0092-8674(00)81959-5 · Cited by 2,790
Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway
HEINRICH, P. C., BEHRMANN, I., MÜLLER-NEWEN, G., SCHAPER, F., & GRAEVE, L. (1998) · Biochemical Journal · doi:10.1042/bj3340297 · Cited by 2,130
Self-citationA family of cytokine-inducible inhibitors of signalling
Starr, R., Willson, T. A., Viney, E. M., Murray, L. J. L., Rayner, J. R., Jenkins, B. J., Gonda, T. J., Alexander, W. S., Metcalf, D., Nicola, N. A., et al. (1997) · Nature · doi:10.1038/43206 · Cited by 2,066
A new protein containing an SH2 domain that inhibits JAK kinases
Endo, T. A., Masuhara, M., Yokouchi, M., Suzuki, R., Sakamoto, H., Mitsui, K., Matsumoto, A., Tanimura, S., Ohtsubo, M., Misawa, H., et al. (1997) · Nature · doi:10.1038/43213 · Cited by 1,408
Interleukin-6 family of cytokines and gp130.
Kishimoto, T., Akira, S., Narazaki, M., & Taga, T. (1995) · Blood · doi:10.1182/blood.v86.4.1243.bloodjournal8641243 · Cited by 1,362
O’Shea, J. J., Gadina, M., & Schreiber, R. D. (2002) · Cell · doi:10.1016/s0092-8674(02)00701-8 · Cited by 1,137
Structure and function of a new STAT-induced STAT inhibitor
Naka, T., Narazaki, M., Hirata, M., Matsumoto, T., Minamoto, S., Aono, A., Nishimoto, N., Kajita, T., Taga, T., Yoshizaki, K., et al. (1997) · Nature · doi:10.1038/43219 · Cited by 1,040
Crystal Structure of the Tyrosine Phosphatase SHP-2
Hof, P., Pluskey, S., Dhe‐Paganon, S., Eck, M. J., & Shoelson, S. E. (1998) · Cell · doi:10.1016/s0092-8674(00)80938-1 · Cited by 997
Specific Inhibition of Stat3 Signal Transduction by PIAS3
Chung, C. D., Liao, J., Liu, B., Rao, X., Jay, P., Berta, P., & Shuai, K. (1997) · Science · doi:10.1126/science.278.5344.1803 · Cited by 980
Cited by
Sorted by citations
Items 2,101–2,200 of 3,269
Embryonic-Like Regenerative Phenomenon: Wound-Induced Hair Follicle Neogenesis
Gong, L., Xu, X., & Li, Y.-H. (2018) · Regenerative Medicine · doi:10.2217/rme-2018-0028 · Cited by 11
Wang, K., Li, Y., Song, N., Che, X., Hou, K., Xu, L., Bai, M., Wang, Q., Wang, Y., Zhou, Y., et al. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27808 · Cited by 9
“Previous reports have shown that IL‐6 is a central player in inhibiting apoptosis and accelerating cell proliferation.(28) As STAT3 is activated by many cytokines and growth factors, including IL‐6, the regional cytokine microenvironment may play an important role in colon cancer.”
BackgroundThe STATus of STAT3 in Lung Cell Senescence?
Adnot, S., Lipskaia, L., & Bernard, D. (2019) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2019-0013ed · Cited by 11
“and growth factor receptors, such as the gp130/IL6 receptor, vascular endothelial growth factor, platelet-derived growth factor, and G protein–coupled receptor ligands (10, 11).”
Jiang, Y., Li, Y., Cheng, J., Ma, J., Li, Q., & Pang, T. (2020) · British Journal of Haematology · doi:10.1111/bjh.16253 · Cited by 11
Cai, K., Li, H., Li, P., Guo, Z., & Yang, Y. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.8504 · Cited by 11
“The JAK‐signal transducer and STAT circuit is activated by IL‐6 via the broad spectrum receptor gp130 and the specific IL‐6Rα co‐receptor (21).”
BackgroundChen, M.-X., Liu, Q., Chen, M.-X., Lei, L., Lin, A., Lei, L., Hui, T. C. K., Li, Q., Ao, L., & Sham, P. C. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.276358 · Cited by 11
“We and others have demonstrated that mitogen-activated protein kinase and the JAK/STAT pathways are disrupted when exposed to inflammation (i.e., lipopolysaccharide, PolyI:C, or IL-6) in vivo and in vitro (Heinrich et al., 2003; Deng et al., 2011; Minogue et al., 2012).”
BackgroundStojković, L., Jovanović, I. B., Živković, M., Zec, M. M., Djurić, T., Životić, I., Kuveljić, J., Kolaković, A., Kolić, I., Djordjević, A., et al. (2020) · Nutrients · doi:10.3390/nu12051484 · Cited by 11
“OSM is an IL6-type cytokine that has both pro- and anti-inflammatory properties [38].”
BackgroundAbdolalian, M., Ebrahimi, M., Aghamirzadeh, M., Eshraghi, N., Moghaddasi, M., & Eslamnik, P. (2021) · Journal of Molecular Histology · doi:10.1007/s10735-021-09989-7 · Cited by 11
Srivastava, T., Joshi, T., Heruth, D. P., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-92751-6 · Cited by 11
Gp130 is expressed in pancreatic cancer and can be targeted by the small inhibitor molecule SC144
Pozios, I., Hering, N. A., Guenzler, E., Arndt, M., Elezkurtaj, S., Knösel, T., Bruns, C. J., Margonis, G. A., Beyer, K., & Seeliger, H. (2022) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-022-04518-9 · Cited by 11
CD70–CD27 ligation between neural stem cells and CD4+ T cells induces Fas–FasL-mediated T-cell death
Lee, E. M., Hurh, S., Cho, B., Oh, K., Kim, S. U., Surh, C. D., Sprent, J., Yang, J., Kim, J. Y., & Ahn, C. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt206 · Cited by 11
“Therefore, IL-6 might require NSC self-renewal and progenitor cell division and differentiation [40-42].”
BackgroundHelicobacter pylori Induces Expression and Secretion of Oncostatin M in Macrophages In Vitro
Zeaiter, Z., Díaz, H., Stein, M., et al. (2010) · Digestive Diseases and Sciences · doi:10.1007/s10620-010-1341-z · Cited by 11
“IL-6 exerts its action via the signal transducer gp 130 receptor leading to the activation of the JAK/STAT and MAPK (mitogen-activated protein kinase) cascades [22].”
BackgroundOncostatin M synergistically inhibits HCV RNA replication in combination with interferon‐α
Ikeda, M., Mori, K., Ariumi, Y., et al. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.03.054 · Cited by 11
“We tested the activity of LIF and IL-6 on HCV RNA replication.”
BackgroundInfluentialShimazaki, T., & Okano, H. (2016) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2015.14 · Cited by 11
“MIR-17/106 The initiation of gliogenesis by NSCs proceeds in two steps: acquisition of gliogenic competence and induction of differentiation.5,21 In the developing mammalian CNS, NSCs acquire gliogenic competence at midgestation, and subsequently oligodendrogliogenesis begins.22 Astrocytic differentiation can be detec…”
BackgroundRiccio, A., Postiglione, L., Sabatini, P., et al. (2012) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463201202500132 · Cited by 11
Liu, Y., & Guo, Z. (2016) · Amino Acids · doi:10.1007/s00726-016-2220-5 · Cited by 11
Zacharaki, D., Ghazanfari, R., Li, H., Lim, H. C., & Scheding, S. (2018) · European Journal Of Haematology · doi:10.1111/ejh.13079 · Cited by 11
Veselá, I., Kotasová, H., Jankovská, S., Procházková, J., & Pachernı́k, J. (2010) · Folia Biologica · doi:10.14712/fb2010056040165 · Cited by 11
“Generally, STAT3 and ERK signalling pathways are two major downstream effectors of activated gp130 (Heinrich et al., 2003).”
BackgroundRole of depression-mediated alterations in pro-inflammatory cytokines in carcinogenesis
Cao, R., Jiang, H., Chen, P., & Dai, C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1659153 · Cited by 12
Shan, W., Xu, J., & Assaraf, Y. G. (2026) · Targetome · doi:10.48130/targetome-0026-0001 · Cited by 11
Li, Y., Zhao, J., Yin, Y., Zhang, C., Zhang, Z., & Zheng, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512210 · Cited by 10
“In response to IL-6 stimulation, signal transducer and activator of transcription 3 (STAT3) proteins are recruited and phosphorylated, and then the homodimerized STAT3 translocates to the nucleus, where it triggers the transcription of various target genes, including cellular differentiation, apoptosis, angiogenic fac…”
BackgroundKumar, S., Arwind, D. A., Harish Kumar., B., Pandey, S., Nayak, R., Vithalkar, M. P., Kumar, N., & Pai, K. S. R. (2024) · Translational Oncology · doi:10.1016/j.tranon.2024.102023 · Cited by 13
“STAT3 β is a distinct isoform of STAT3 that differs from STAT3 α by the replacement of the C-terminal trans-activation domain with a unique 23-amino acid sequence [21].”
BackgroundZhang, J., Yu, M., Zhang, T., Song, X., Ying, S., Shen, Z., & Yu, C. (2024) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjae134 · Cited by 13
Castorina, A., Scheller, J., Keay, K. A., Marzagalli, R., Rose‐John, S., & Campbell, I. L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179453 · Cited by 10
Valencia‐Ortega, J., Castillo-Santos, A., Molerés-Orduña, M., Solis‐Paredes, J. M., Saucedo, R., Estrada‐Gutiérrez, G., & Camacho‐Arroyo, I. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111655 · Cited by 10
Song, Y., Zhang, X., Han, X., Wang, G., Wang, M., Wu, H. M., & Wu, X. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.119448 · Cited by 10
Tocci, D. R., Fogel, M., Gupta, V., Kim, P. S.-H., Latimer, J. J., Adlimoghaddam, A., Robison, L. S., & Albensi, B. C. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01706-w · Cited by 13
“NRTKs can also control gene activity, such as the activation of the signal transducer and activator of transcription (STAT) through IL-6-induced phosphorylation of the membrane-bound TK, Janus kinase [26].”
Albano, F., Severini, F. L., Calice, G., Zoppoli, P., Falco, G., & Notarangelo, T. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.167821 · Cited by 10
Hidalgo-Cantabrana, C., Kekkonen, R. A., Reyes‐Gavilán, C. G. D. L., Salminen, S., Korpela, R., Gueimonde, M., & Ruas‐Madiedo, P. (2013) · Journal of Functional Foods · doi:10.1016/j.jff.2013.11.001 · Cited by 10
Haas, C., Maywald, M., Goetzenich, A., et al. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.5a0417-143r · Cited by 10
Serrano, A., Ros, G., & Nieto, G. (2019) · Antioxidants · doi:10.3390/antiox8080286 · Cited by 10
“Although the control ham showed slight inhibition of IL-1β, IL-6, and TNFα, the inhibition of these cytokines was significantly higher for the hams reformulated with polyphenol blends (p < 0.0001).”
BackgroundInfluentialde Oliveira, P. H. C., Gomes‐Filho, J. E., Rodrigues, M. J. D. S., et al. (2022) · International Endodontic Journal · doi:10.1111/iej.13795 · Cited by 10
IL-6/STAT3 Signaling Axis Enhances and Prolongs Pdcd1 Expression in Murine CD8 T Cells
Powell, M. D., Lu, P., Neeld, D. K., Kania, A. K., George-Alexander, L.-E., Bally, A. P. R., Scharer, C. D., & Boss, J. M. (2022) · ImmunoHorizons · doi:10.4049/immunohorizons.2100112 · Cited by 10
Cytokines Regulating Trophoblast Invasion
Fitzgerald, J. S., Abad, C., Álvarez, Á. M., Mehta, R. B., Chaiwangyen, W., Dubinsky, V., Silva, B. G., Gutiérrez, G., Hofmann, S., Hölters, S., et al. (2011) · Advances in Neuroimmune Biology · doi:10.3233/nib-2011-023 · Cited by 11
“The murine and human G-CSF protein show almost complete cross-reactivity regarding biological effects and receptor-binding in human or murine normal and leukaemic cells [93–97].”
BackgroundInterleukin 11: similar or opposite roles in female reproduction and reproductive cancer?
Winship, A., Menkhorst, E. M., Sinderen, M. L. V., & Dimitriadis, E. (2014) · Reproduction Fertility and Development · doi:10.1071/rd14128 · Cited by 10
“STAT3 activation is known to regulate target genes associatedwith cellular invasion, proliferation and/or survival (Pensa et al. 2009).”
BackgroundInfluentialLau, W. K. W., Mak, J., Chan, K., & Law, A. (2011) · Neurotoxicity research · doi:10.1007/s12640-011-9301-8 · Cited by 11
Amin, O. A. I., & Salah, H. E. (2011) · Egyptian Journal of Anaesthesia · doi:10.1016/j.egja.2011.04.005 · Cited by 10
Soliman, M. M. (2013) · American Journal of Immunology · doi:10.3844/ajisp.2013.148.158 · Cited by 9
“Several cytokines are produced by various cells and tissues in response to infection and/or toxicity as TiO2 such as IL-6, IL-8 and IL-10.”
BackgroundInfluentialGürkan, A., Becerik, S., Öztürk, V. Ö., Atmaca, H., Atilla, G., & Emingil, G. (2015) · Journal of Periodontology · doi:10.1902/jop.2015.150003 · Cited by 10
Endocytosis of pro-inflammatory cytokine receptors and its relevance for signal transduction
Hermanns, H. M., Wohlfahrt, J., Mais, C., Hergovits, S., Jahn, D., & Geier, A. (2016) · Biological Chemistry · doi:10.1515/hsz-2015-0277 · Cited by 13
“IL-6 signals via a cytokine receptor containing a conserved membrane-proximal proline-rich region denominated box 1 region and required for the recruitment of Janus family tyrosine kinases (Heinrich et al., 2003).”
BackgroundSelf-citationLiao, S., Li, P., Wang, J., et al. (2016) · RSC Advances · doi:10.1039/c6ra17380b · Cited by 10
Эволюционная пластичность цитокинов семейства IL-6
Gorshkova, E. A., Недоспасов, С. А., & Shilov, E. S. (2016) · Molecular Biology · doi:10.7868/s0026898416060069 · Cited by 10
Pattamaprapanont, P., Muanprasat, C., Soodvilai, S., Srimaroeng, C., & Chatsudthipong, V. (2016) · The Review of Diabetic Studies · doi:10.1900/rds.2016.13.197 · Cited by 10
Sen, M., Johnston, P., Pollock, N. I., DeGrave, K. A., Joyce, S., Freilino, M. L., Hua, Y., Camarco, D. P., Close, D. A., Huryn, D., et al. (2017) · Journal of chemical biology · doi:10.1007/s12154-017-0169-9 · Cited by 12
“In classical IL-6 signal transduction, IL-6 binds to IL-6 receptor alpha subunits (IL-6Rα, gp80) on cells that express this receptor, and this binary complex then recruits a gp130 signaling subunit to form an IL-6/IL-6Rα/gp130 heterotrimer and then two of these interact to form a hexamer-activated IL-6/ IL-6Rα/gp130 s…”
BackgroundInfluentialDiarylheptanoids from Curcuma phaeocaulis Suppress IL-6-Induced STAT3 Activation
Jang, H., Park, E.-J., Lee, S., et al. (2018) · Planta Medica · doi:10.1055/a-0668-0962 · Cited by 10
“Binding of IL-6 to the IL-6 receptor complex, consisting of IL6Rα and glycoprotein 130 (gp130), leads to the activation of Janus kinase family members (JAKs) responsible for the dimerization of the STAT3 protein [10].”
BackgroundEmerging technologies in protein interface engineering for biomedical applications
Krohl, P. J., Ludwig, S. D., & Spangler, J. B. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.01.017 · Cited by 10
The Network of Inflammatory Mechanisms in Lupus Nephritis
Nozaki, Y. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.591724 · Cited by 11
IL-6 promotes MYC-induced B cell lymphomagenesis independent of STAT3
Petrenko, O., Li, J., Cimica, V., Mena, P., Shin, H. Y., D’Amico, S., & Reich, N. C. (2021) · PLoS ONE · doi:10.1371/journal.pone.0247394 · Cited by 10
“Tyrosine phosphorylation of the receptor creates docking sites for the STAT transcription factors and for SH2 domain adaptor proteins involved in activation of MAPK/ERK and PI3K/AKT signaling [6,7].”
BackgroundMolecular Diagnosis of Prosthetic Joint Infection
Esteban, J., Molina‐Manso, D., del Prado, G., & Gómez‐Barrena, E. (2012) · Springer eBooks · doi:10.1007/978-1-4471-2482-5_19 · Cited by 10
“IL-6, IL-1 b , and TNFa belong to an important family of mediators involved in the regulation of the acute-phase response to injury and infection [ 31 ] , and their increased levels are intimately related to elevations of acute-phase proteins like CRP [ 32, 33 ] .”
BackgroundMechanisms and factors in embryonic stem cell self-renewal
Chambers, I. (2005) · RENDICONTI LINCEI · doi:10.1007/bf02904758 · Cited by 10
Deutscher, N., Bataille, F., Hausmann, M., Kießling, S., Müller‐Newen, G., Leeb, S. N., Herfarth, H. H., Heinrich, P. C., Schölmerich, J., & Rogler, G. (2005) · International Journal of Colorectal Disease · doi:10.1007/s00384-005-0055-8 · Cited by 10
“tivator of transcription (Jak-STAT) pathway [4, 5].”
Self-citationSIPAR negatively regulates STAT3 signaling and inhibits progression of melanoma
Ren, F., Su, F., Ning, H., Wang, Y., Geng, Y., Feng, Y., Wang, Y., Zhang, Y., Jin, Z. H., Li, Y., et al. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.07.023 · Cited by 10
Kaczmarek, M. M., Krawczynski, K., Szuszkiewicz, J., et al. (2014) · Reproductive Biology · doi:10.1016/j.repbio.2014.06.003 · Cited by 10
La interleucina 6 en la fisiopatología de la artrirtis reumatoide
Álvarez, J. (2009) · Reumatología Clínica · doi:10.1016/s1699-258x(09)70203-7 · Cited by 8
Wallerstedt, E., Sandqvist, M., Smith, U., & Andersson, C. X. (2011) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-011-0738-0 · Cited by 11
“This allows STAT3 to become phosphorylated on Tyr-705, which is necessary for the homo- or hetero-dimerization of STAT3 and STAT1 and this, in turn, is a prerequisite for the nuclear translocation of the STAT molecules [14].”
BackgroundCiliary neurotrophic factor enhances nicotinic synaptic transmission in sympathetic neurons
Nai, Q., Wang, X., Jin, Y. H., Sun, D., Li, M., Hu, B., & Zhang, X. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22260 · Cited by 10
Liu, P., Zhao, L., Xu, X., Liu, F., Zhang, W., Zhou, C., Chen, J., Pan, Y., Du, Y., Yang, J., et al. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.07.043 · Cited by 10
“Briefly, IL-6 induces STAT3 activation through the IL-6R/gp130/JAK pathway [38], while IFN-γ induces STAT3 activation through the type II-receptor/JAK pathway [39].”
BackgroundThe upregulation of oncostatin M in inflamed human dental pulps
Huang, F., Tsai, C., Yang, S., & Chang, Y. (2009) · International Endodontic Journal · doi:10.1111/j.1365-2591.2009.01567.x · Cited by 10
Gavito, A., Cabello, R., Suárez, J., Serrano, A., Pavón, F. J., Vida, M., Romero, M. D. M., Pardo, V., Bautista, D., Arrabal, S., et al. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13423 · Cited by 10
“IL-6 belongs to the family of IL-6-type cytokines (Heinrich et al., 2003; Qu et al., 2014).”
BackgroundMeyer, M. K., & Andersen, M. (2015) · Journal of Proteomics & Bioinformatics · doi:10.4172/jpb.1000380 · Cited by 10
“The JAK/STAT pathways acts by activating the kinases Jak1, Jak2, and Tyk2, which in turn phosphorylates STAT1, STAT3, and STAT5 [20,21].”
BackgroundAction of Administered Ciliary Neurotrophic Factor on the Mouse Dorsal Vagal Complex
Senzacqua, M., Severi, I., Perugini, J., Acciarini, S., Cinti, S., & Giordano, A. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00289 · Cited by 10
“In wild-type mice, CNTF treatment for 45min induced STAT3, STAT1, and STAT5 phosphorylation in neurons as well as glial cells of the area postrema; here, the majority of CNTF-responsive cells activated multiple STAT isoforms, and a significant proportion of CNTF-responsive glial cells bore the…”
BackgroundCold-Induced Sweating Syndrome Including Crisponi Syndrome
Hahn, A. F., & Boman, H. (2016) · Europe PMC (PubMed Central) · Cited by 10
Blaszczak, W., White, B., Monterisi, S., & Swietach, P. (2024) · Cell Reports · doi:10.1016/j.celrep.2023.113612 · Cited by 9
Chou, C., Hua, K., Chen, M., Wu, C., Hsu, C., Wang, J., Hsiao, M., & Wei, L. (2022) · mAbs · doi:10.1080/19420862.2022.2029675 · Cited by 9
“mitogen-activated protein kinase (MAPK) signaling cascade.(17) This so-called classic signaling is relevant only in a few cell types (hepatocytes, some epithelial cells, and leukocytes) that express IL-6Rα.”
BackgroundCarmi, Y. K., Khamaisi, H., Adawi, R., Noyman, E., Gopas, J., & Mahajna, J. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24097730 · Cited by 8
“IL-6 is a pro-inflammatory cytokine produced by a number of cell types, including a variety of immune cells that affect target cells such as ovarian cancer cells via the JAK/STAT pathway [43].”
BackgroundPark, Y., Choo, S. P., Jung, G. S., Kim, S. H., Lee, M. J., Im, W., Park, H., Lee, I., Lee, J. H., Cho, S., et al. (2023) · Nutrients · doi:10.3390/nu15133001 · Cited by 10
“STAT3, a member of the STAT (signal transducer and activator of transcription pathway) family, was phosphorylated by Janus kinase (JAK), and it could promote proliferation, angiogenesis, and regulate tumor microenvironment [26,27].”
BackgroundDao, B. N., Le, H., Nguyen, K. X., et al. (2023) · Pneumon · doi:10.18332/pne/170181 · Cited by 9
Autocrine Regulation of Interleukin-6 via the Activation of STAT3 and Akt in Cardiac Myxoma Cells
Jougasaki, M., Takenoshita, Y., Umebashi, K., Yamamoto, M., Sudou, K., Nakashima, H., Sonoda, M., & Kinjo, T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042232 · Cited by 9
“…(IL-6R) and subsequent recruitment of the transmembrane gp130, activating the intracellular signal transduction system, including Janus kinase (JAK)-signal transducer and activator of transcription (STAT) 3, phosphatidylinositol-3-kinase (PI3K)/Akt, and mitogen-activated protein kinase [3].”
BackgroundCrosstalk between lipocalin-2 and IL-6 in traumatic brain injury: Closely related biomarkers
Kim, J., Jeong, H., Hyeon, S. J., Park, U., Oh, W., Hwang, J., Lim, H., Ko, P., Lee, H., Lee, W., et al. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.115092 · Cited by 9
King, Z., Desai, S. R., Frank, D. A., & Shastri, A. (2025) · Neoplasia · doi:10.1016/j.neo.2025.101137 · Cited by 11
“Furthermore, growth factors (e.g., GM-CSF, G-CSF) and cytokines (e.g., IL-3, IL-6) activate signaling pathways such as JAK/STAT, MAPK, and PI3K/AKT, which regulate transcription factor activity[40 – 43].”
Leptin and Insulin in COPD: Unveiling the Metabolic-Inflammatory Axis—A Narrative Review
Catană, O. M., Nemeş, A. F., Cioboată, R., Toma, C., Mitroi, D. M., Călăraşu, C., & Streba, C. T. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14082611 · Cited by 11
“The signaling of other cytokines in the IL-6 family is also characterized by the activation of these pathways [48].”
Inflammatory factors collaboratively link Helicobacter pylori-induced gastritis to gastric cancer
Zhang, M., Su, A., Song, H., Zhang, S., Deng, Y., Jing, W., Guo, J., Zhan, W., Ma, Y., & Hu, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1628543 · Cited by 15
Inflame and restrain — the paradoxical roles of IL-12 and IL-23 in immunity
Rindlisbacher, L., Navarro, M. N., & Becher, B. (2026) · Nature reviews. Immunology · doi:10.1038/s41577-025-01255-1 · Cited by 18
“For example, IL-6 promotes the acute phase response, enhances T cell proliferation and supports IL-17A-producing helper T (T H 17) cell differentiation 148–150 .”
IL-6/STAT3 signaling in prostate cancer: CAF-driven immune evasion and therapeutic opportunities
Zhou, T., Li, Y., Liu, Z., Zeng, Z., Li, T., Chen, L., Zhao, H., Wu, X., Shen, Y., Fan, H., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1736606 · Cited by 10
Prayong, P., Mairiang, E., Pairojkul, C., et al. (2014) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2014.15.13.5443 · Cited by 9
“Functional activity of IL-6 on the target cells occurs by binding to IL-6-specific receptor (IL-6R) both a membrane-bound (mIL-6R) and soluble form (sIL-6R) together with gp130 (Heinrich et al., 1998; 2003).”
BackgroundWaldron, P. R., Belitskaya‐Lévy, I., Chary, A., et al. (2016) · Journal of Immunology Research · doi:10.1155/2016/6530436 · Cited by 9
“IL-6 is known as a marker of host inflammatory response and has been thought of as a mediator of innate immunity via its receptor interactions with gp130 and resulting proinflammatory transcriptional activity via both the JAK/STAT pathway and extracellular-signal-regulated kinase/mitogenactivated protein kinase (ERK/M…”
Wang, F., Wei, F., Liu, H., et al. (2020) · Immunological Investigations · doi:10.1080/08820139.2020.1793775 · Cited by 9
“It is an important cytokine that mediates numerous inflammatory and immunomodulatory pathways and is implicated in multiple diseases, including Alzheimer’s disease, Type 2 diabetes, arteriosclerosis, osteoporosis, a variety of tumors, and some immune reactions like systemic lupus erythematosus (SLE) and ankylosing spo…”
BackgroundPanting, M., Holme, I. B., Björnsson, J. M., et al. (2021) · Frontiers in Plant Science · doi:10.3389/fpls.2021.755788 · Cited by 9
Clowers, M. J., & Moghaddam, S. J. (2022) · Cancers · doi:10.3390/cancers14071785 · Cited by 9
Interval-Based Secretomics Unravels Acute-Phase Response in Hepatocyte Model Systems
Knecht, S., Eberl, H. C., & Bantscheff, M. (2022) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2022.100241 · Cited by 8
“There is a growing body of evidence that suggests that IL6 is the main inducer of the APR whereas IL1-like cytokines seem to play a modulating role by inhibiting or enhancing the expression of various proteins (6, 8, 116–118), most likely through interaction between NF-kB and STAT3 signaling.”
BackgroundREMOVED: Natural products as modulators of signaling in inflammation
Daniyal, M., & Wang, W. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819218-4.00005-5 · Cited by 8
IL-6-Driven pSTAT1 Response Is Linked to T Cell Features Implicated in Early Immune Dysregulation
Lambert, K., Diggins, K. E., Jones, B. E., Hundhausen, C., Maerz, M. D., Hocking, A. M., Sanda, S., Greenbaum, C. J., Linsley, P. S., Cerosaletti, K. M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.935394 · Cited by 9
“Formation of the IL-6/IL-6R/gp130 complex initiates intracellular signaling via the JAK/STAT pathway, driving phosphorylation of STAT1 and STAT3 proteins (20).”
BackgroundInfluentialMa, Y., Huang, Y., & Xu, G. (2023) · QJM · doi:10.1093/qjmed/hcac287 · Cited by 8
Role of SOCS and VHL Proteins in Neuronal Differentiation and Development
Kanno, H., Matsumoto, S., Yoshizumi, T., Nakahara, K., Kubo, A., Murata, H., Shuin, T., & Hoi-Sang, U. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043880 · Cited by 9
Reyes-Ramos, C. A., Ramírez-Jirano, L. J., Bitzer-Quintero, O. K., Vázquez‐Medina, J. P., Gaxiola‐Robles, R., & Zenteno‐Savín, T. (2023) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2023.111438 · Cited by 9
Interleukin-6 stimulates in vitro development of late-stage ovine embryos
Javvaji, P. K., Francis, J. R., Dhali, A., Kolte, A. P., Mech, A., Roy, S. C., & Mishra, A. (2023) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2023.104133 · Cited by 9
CNP-miR146a Decreases Inflammation in Murine Acute Infectious Lung Injury
Vaughn, A. E., Lehmann, T., Sul, C., et al. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15092210 · Cited by 9
“Additionally, IL-6 is an early acute phase reactant critical to the regulation of the acute-phase response to injury and infection [34].”
BackgroundWoods, A. M., McIlmoil, C. J., Rankin, E. N., Packer, A. A., Stevens, J. C., Macievic, J. A., Brown, A. B., Porter, J. P., & Judd, A. M. (2008) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2008.05.005 · Cited by 9
A novel OSMR mutation in familial primary localized cutaneous amyloidosis in a Japanese family
Arita, K., Abe, R., Baba, K., et al. (2009) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2009.03.003 · Cited by 9
Nowak, M. M., Wyczałkowska-Tomasik, A., Włodarczyk, Z., et al. (2012) · Cytokine · doi:10.1016/j.cyto.2012.04.041 · Cited by 9
Exploring genetic susceptibility to obesity through genome functional pathway analysis
Gabrielli, A. P., Manzardo, A. M., & Butler, M. G. (2017) · Obesity · doi:10.1002/oby.21847 · Cited by 11
“IL-6 is a cytokine involved in immunoregulation and management of inflammation (18).”
BackgroundStella Sravanthi, V., Palaka, B. K., vel, G., et al. (2019) · Process Biochemistry · doi:10.1016/j.procbio.2019.04.018 · Cited by 9
Basu, A., Das, A. S., Borah, P. K., Duary, R. K., & Mukhopadhyay, R. (2020) · Inflammation Research · doi:10.1007/s00011-020-01387-1 · Cited by 9
Yoo, B. Y., Kim, S., Shin, B. H., Lee, M. H., Choy, Y. B., Lee, K., Heo, C. Y., & Koh, W. (2020) · Journal of Industrial and Engineering Chemistry · doi:10.1016/j.jiec.2020.12.015 · Cited by 9
Maghbooli, Z., Moghadasi, A. N., Rezaeimanesh, N., Omidifar, A., Varzandi, T., & Sahraian, M. A. (2021) · BMC Neurology · doi:10.1186/s12883-021-02198-5 · Cited by 9
“Within the metabolic pathways, it has impairing effects on the insulin signaling which could result in IR and related diseases [39, 48] via NF-kB signaling.”
BackgroundRowinski, J. R., Rispoli, L. A., Payton, R. R., et al. (2020) · Animal Reproduction · doi:10.1590/1984-3143-ar2020-0221 · Cited by 9
“Although receptor binding is important, intracellular signaling related to IL6 is dependent on forming a complex with IL6 signal transducer (Hibi et al., 1990; Mackiewicz et al., 1992; Heinrich et al., 2003; Wolf et al., 2014).”
BackgroundSuppression of multiple myeloma by mitochondrial targeting
Aisen, Y., Gatt, M. E., Hertz, R., Smeir, E., & Bar‐Tana, J. (2021) · Scientific Reports · doi:10.1038/s41598-021-83829-2 · Cited by 9
Bioactive recombinant human oncostatin M for NMR-based screening in drug discovery
Mass, O. A., Tuccinardi, J. P., Woodbury, L. G., Wolf, C. L., Grantham, B., Holdaway, K. A., Pu, X., King, M. D., Warner, D. L., Jorcyk, C. L., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-95424-6 · Cited by 9
Kanda, R., Miyagawa, Y., Wada‐Hiraike, O., et al. (2021) · Heliyon · doi:10.1016/j.heliyon.2021.e08696 · Cited by 9
“Research has established that OSM binding to the OSM receptor (OSMR) shows a wide variety of physiological actions via induction of the JAK (Janus kinase)/STAT (signal transducer and activator of transcription) and Ras/ERK (extracellular signal–regulated kinase) signaling pathways [13, 14].”
BackgroundEl-Sonbaty, S. M., & Araby, E. (2014) · Journal of Radiation Research and Applied Sciences · doi:10.1016/j.jrras.2013.12.001 · Cited by 9
Metadata
- Authors
- HEINRICH, P. C., BEHRMANN, I., HAAN, S., HERMANNS, H. M., MÜLLER-NEWEN, G., & SCHAPER, F.
- Affiliations
- Universitätsklinikum Aachen (DE)
- Institut für Biochemie, RWTH Aachen, Universitätsklinikum, Pauwelsstrasse 30, D-52074 Aachen, Germany
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2003-08-15
- Volume
- 374
- Issue
- 1
- Pages
- 1-20
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1223585
- OpenAlex
- W2086840459
- Cited by
- 3,272
- References
- 265
- Citations by year
- 2026: 70 · 2025: 114 · 2024: 106 · 2023: 121 · 2022: 138 · 2021: 146 · 2020: 129 · 2019: 151 · 2018: 141 · 2017: 141 · 2016: 176 · 2015: 157 · 2014: 171 · 2013: 190 · 2012: 179
- FWCI
- 50.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- cytokine signaling, gp130, LIF receptor, OSM receptor, JAK/STAT signaling, MAPK signaling, protein tyrosine phosphatase, suppressor of cytokine signaling, PIAS, signal termination, signal transduction, acute phase response, inflammation, rheumatoid arthritis, multiple myeloma, prostate cancer
- MeSH terms
- Animals, Humans, Infections, Models, Molecular, Phosphorylation, Protein Conformation, Wounds and Injuries, Signal Transduction, Interleukin-6, Cytokines, Protein Structure, Secondary, Receptors, Interleukin-6
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-23, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-23 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
