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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
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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.
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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“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
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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
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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
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- Not matchedcites [45]
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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- Not matchedcites [55]
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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
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- Not matchedcites [59]
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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
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- Not matchedcites [49]
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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.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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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
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Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
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Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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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
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- Not matchedcites [108]
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- 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.
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably 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.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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?
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Strength:plain· not yet calibratedn = 8Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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.
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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.
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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.”
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“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
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Items 1,701–1,800 of 3,269
Characterization of the Interleukin (IL)-6 Inhibitor IL-6-RFP
Metz, S., Wiesinger, M., Vogt, M., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606885200 · Cited by 21
Self-citationGallucci, R. M., Sloan, D. K., O'Dell, S. J., & Reinke, L. A. (2004) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000118316.20560.0d · Cited by 21
Conrad, M. F., Albadawi, H., Stone, D. H., et al. (2006) · Journal of Surgical Research · doi:10.1016/j.jss.2006.04.027 · Cited by 21
Enhancer-dependent inhibition of mouse renin transcription by inflammatory cytokines
Li, P., Wang, Y., Jones, C. A., Glenn, S. T., Baumann, H., & Gross, K. W. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00333.2003 · Cited by 21
May, P., Schniertshauer, U., Gerhartz, C., Horn, F., & Heinrich, P. C. (2003) · Acta Biochimica Polonica · doi:10.18388/abp.2003_3653 · Cited by 21
“As mentioned above, IL-6 has been reported to activate three different STAT factors, as well as signaling networks different from the JAK/STAT pathway (for a review see Heinrich et al., 2003).”
BackgroundSelf-citationMolecular pathway of pancreatic cancer‐associated neuropathic pain
Giri, S. S., Tripathi, A. S., Erkekoğlu, P., & Zaki, M. E. A. (2024) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.23638 · Cited by 21
Lin, X., Li, X., Zhai, Z., & Zhang, M. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1563286 · Cited by 24
Cardiotrophin-1 is inversely associated with obesity in non-diabetic individuals
Hung, H., Lu, F., Wu, H., et al. (2015) · Scientific Reports · doi:10.1038/srep17438 · Cited by 20
Wang, X., Wang, Y., Xiao, G., Wang, J., Zu, L., Hao, M., Sun, X., Fu, Y., Hu, G., & Wang, J. (2016) · Oncotarget · doi:10.18632/oncotarget.8734 · Cited by 20
Lü, P., Wu, F. ‐., Rong, Z., Fang, C., Deng, C., Bin, L., & Yang, B. (2019) · Clinical and Experimental Dermatology · doi:10.1111/ced.13925 · Cited by 20
EC330, a small-molecule compound, is a potential novel inhibitor of LIF signaling
Yue, X., Wu, F., Wang, J., Kim, K., Santhamma, B., Dileep, K. V., Zhang, K. Y. J., Viswanadhapalli, S., Vadlamudi, R. K., Ahmed, G., et al. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa008 · Cited by 20
Immune Microenvironment: New Insight for Familial Adenomatous Polyposis
Yang, J. H., Wen, Z., Li, W., Sun, X., Ma, J., She, X., Zhang, H., Tu, C., Wang, B., Huang, D., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.570241 · Cited by 20
Refaie, M. M. M., Shehata, S., Bayoumi, A. M. A., et al. (2021) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-021-07214-x · Cited by 20
“Therefore, modulation of the IL-6/STAT signaling pathway represents an essential strategy for the treatment of 5FU-induced cardiac injury [5, 7, 8].”
BackgroundZhu, H., Liu, X., Ding, Y., Tan, K., Ni, W., Ouyang, W., Tang, J., Ding, X., Zhao, J., Hao, Y., et al. (2022) · Stem Cell Research & Therapy · doi:10.1186/s13287-021-02675-1 · Cited by 19
“All IL-6 family members are involved in dimerization of the subunits of gp130 to initiate the downstream signaling by activation of Janus kinases and subsequent phosphorylation of cytoplasmic tyrosine residues, resulting in engagement of the tyrosine phosphatase Shp2 and activation of the downstream Ras/Erk and PI3K/A…”
BackgroundHuo, Y., Yang, J., Zheng, J.-H., Xu, D., Yang, M., Tao, L., Yao, H., Fu, X., Yang, J., Liu, D., et al. (2022) · Cell Proliferation · doi:10.1111/cpr.13237 · Cited by 20
“which gp130 binds, forming a complex consisting of two IL-6, two IL6R and two gp130 molecules(18); alternativly, IL-6 trans-signalling that follows the classical pathway except that IL-6 binds soluble IL-6R (sIL6R) rather than mIL-6R can also occur.(19) The third model, termed IL-6”
BackgroundMarklund, M., Schultz, N., Friedrich, S., Berglund, E., Tarish, F., Tanoglidi, A., Liu, Y., Bergenstråhle, L., Erickson, A. M., Helleday, T., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33069-3 · Cited by 19
Zhang, X., Chen, S., Yin, G., Liang, P., Feng, Y., Yu, W., Meng, D., Liu, H., & Zhang, F. (2024) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/10742484241248046 · Cited by 28
“30 Targeting downstream kinases or transcription factors in this pathway has emerged as a potential approach for treating atherosclerosis.”
Unveiling the role of interleukin-6 in pancreatic cancer occurrence and progression
Song, M., Tang, Y., Cao, K., Qi, L., & Xie, K. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1408312 · Cited by 22
Interleukin 6 in the Physiopathology of Rheumatoid Arthritis
Álvarez, J. L. P. (2009) · Reumatología Clínica (English Edition) · doi:10.1016/s2173-5743(09)70086-3 · Cited by 20
Gibb, J., Al‐Yawer, F., & Anisman, H. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.11.004 · Cited by 22
Effects of PEG-Based Thermoresponsive Polymer Brushes on Fibroblast Spreading and Gene Expression
Sefcik, L. S., Kaminski, A., Ling, K., Laschewsky, A., Lutz, J., & Wischerhoff, E. (2013) · Cellular and Molecular Bioengineering · doi:10.1007/s12195-013-0286-7 · Cited by 20
Antunes, M. F. P., Titz, T. O., Batista, I. D. F. C., Marques-Porto, R., Oliveira, C. F., de Araújo, C. A. A., & Macedo-Soares, M. F. (2014) · Journal of Helminthology · doi:10.1017/s0022149x14000200 · Cited by 20
“IL-6 is customarily considered a regulator of acute-phase inflammatory responses and is released in response to IL-1b and TNF-b (Heinrich et al., 2003; Rose-John, 2012).”
BackgroundModifying factors of theHFEhemochromatosis phenotype
Deugnier, Y., & Mosser, J. (2008) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2.4.531 · Cited by 16
Proposals for Bacterial and Fungal Biocontrol Agents
Strauch, O., Strasser, H., Hauschild, R., et al. (2011) · Springer eBooks · doi:10.1007/978-90-481-3664-3_13 · Cited by 20
“and interleukin-6 (Heinrich et al. 2003), which would be also available for mice.”
BackgroundThe Potential of a Novel Class of EPAC-Selective Agonists to Combat Cardiovascular Inflammation
Barker, G., Parnell, E., van Basten, B., Buist, H., Adams, D., & Yarwood, S. J. (2017) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd4040022 · Cited by 20
“IL-6 signalling is ediated by a receptor co plex co prising an α chain (IL-6Rα) and a trans e brane glycoprotein (gp130) that associate on the cell surface in the presence of the cytokine to for a 2:2:2 hetero eric co plex [57].”
BackgroundMuneoka, S., Murayama, S., Nakano, Y., & Miyata, S. (2018) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2018.04.017 · Cited by 20
Interleukin 6: The biology behind the therapy
Jones, S. A., Takeuchi, T., Aletaha, D., Smolen, J. S., Choy, E., & McInnes, I. B. (2018) · Considerations in Medicine · doi:10.1136/conmed-2018-000005 · Cited by 21
“1 9–13 The involvement of IL-6 in these processes is reflected by the impact of IL-6-directed therapies on lipid biosynthesis and anaemia, as well as effects on patients’ well-being including pain, mood, depression, fatigue, and sleep (figure 1).”
BackgroundFarsani, M. A., Kamel, M., Mehrpouri, M., et al. (2018) · Pathology & Oncology Research · doi:10.1007/s12253-018-0536-z · Cited by 20
“On the other hand, interferon (IFN) family, basically involved in host defense against viruses and tumors, could bind to their receptors and through stimulation of jack/stat signaling pathways [9, 10], regulates the expression of diverse genes and protein production participating in inducing cell death in malignant ce…”
BackgroundDo Alarmins Have a Potential Role in Autism Spectrum Disorders Pathogenesis and Progression?
Salvo, E. D., Casciaro, M., Quartuccio, S., Genovese, L., & Gangemi, S. (2018) · Biomolecules · doi:10.3390/biom9010002 · Cited by 20
“Cytokine activation axis like NF-kB, JAK/STAT have a main role in CNS cells proliferation and differentiation particularly during pre-natal development [59].”
BackgroundRichardson, T. G., Fang, S., Mitchell, R. E., Holmes, M. V., & Smith, G. D. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103228 · Cited by 19
“This protein is encoded by the IL6ST gene and is responsible for signal transduction with all members of the interleukin 6 receptor family [46].”
Modulation of matrix metalloproteases by ciliary neurotrophic factor in human placental development
Tossetta, G., Fantone, S., Busilacchi, E. M., et al. (2022) · Cell and Tissue Research · doi:10.1007/s00441-022-03658-1 · Cited by 20
“It belongs to the interleukin (IL)-6 cytokine family along with cardiotrophin-1, IL-6, IL-11, IL-27, leukaemia inhibitory factor (LIF) and oncostatin-M (Heinrich et al. 2003).”
BackgroundQualitative and Quantitative Analysis of a Bio-PEPA Model of the Gp130/JAK/STAT Signalling Pathway
Guerriero, M. L. (2009) · Lecture notes in computer science · doi:10.1007/978-3-642-04186-0_5 · Cited by 20
“The gp130/JAK/STAT signalling pathway is a well-studied biological system, of great clinical interest because of its key role in human fertility, neuronal repair and Qualitative and Quantitative Analysis of a Bio-PEPA Model 93 haematological development [15, 16 ,17].”
BackgroundOberle, S., Schober, A., Meyer, V., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4127-05.2006 · Cited by 20
Gene expression in rabbit appendices infected with Eimeria coecicola
Dkhil, M. A., Abdel-Maksoud, M. A., Al‐Quraishy, S., et al. (2011) · Veterinary Parasitology · doi:10.1016/j.vetpar.2011.11.031 · Cited by 20
Ngamurulert, S., Limjindaporn, T., & Auewaraku, P. (2009) · Acta Virologica · doi:10.4149/av_2009_03_153 · Cited by 20
“Another major signaling pathway for IL-6R is the MAPK (mitogen-activated protein kinase) cascade (Heinrich et al., 2003; Akira et al., 1997).”
BackgroundZhang, Y., Ma, Q., Liu, T., Shi, K., Jiang, K., Wen, Y., Ma, B., Zhou, Y., Fan, Q., & Qiu, X. (2013) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-013-1561-7 · Cited by 20
Hidalgo, E. R., Essex, S. J., Yeo, L., Curnow, J., Filer, A. D., Cooper, M. S., Thomas, A. M. C., McGettrick, H. M., Salmon, M., Buckley, C. D., et al. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30570 · Cited by 20
Juan, T., Bolon, B. N., Lindberg, R. A., Sun, Y. S., Van, G. Y., & Fletcher, F. (2008) · Veterinary Pathology · doi:10.1354/vp.46-1-124 · Cited by 20
Are favorite molecules of endometrial receptivity still in favor?
Aghajanova, L., Simón, C., & Horcajadas, J. A. (2008) · Expert Review of Obstetrics & Gynecology · doi:10.1586/17474108.3.4.487 · Cited by 20
Regulation of Drug-Metabolizing Enzymes and Drug Metabolism by Inflammatory Responses
Morgan, E. T. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802949-7.00002-x · Cited by 20
Role of IL-6 in neuroendocrine differentiation and chemosensitivity of non-small cell lung cancer
Chang, K.-T., Huang, C. F., Tsai, C., et al. (2005) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00033.2005 · Cited by 20
“By acting as an autocrine and paracrine growth factor, IL-6 is able to promote tumor cell proliferation through upregulation of anti-apoptotic and angiogenic proteins in tumor cells (17).”
BackgroundDamiani, C. L., & O'Callaghan, J. P. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04321.x · Cited by 20
Zinc–gene interaction related to inflammatory/immune response in ageing
Mocchegiani, E., & Malavolta, M. (2008) · Genes & Nutrition · doi:10.1007/s12263-008-0085-2 · Cited by 20
“Interleukin-6 is a pleiotropic cytokine capable of regulating proliferation, differentiation and activity of a variety of cell types and plays a pivotal role in immune response [68].”
BackgroundLokau, J., Garbers, Y., Vicente, M. M., Dittrich, A., Meltendorf, S., Lingel, H., Münster-Kühnel, A. K., Brunner-Weinzierl, M. C., & Garbers, C. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1488745 · Cited by 20
Hoover, W. C., Zhang, W., Xue, Z. C., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042601 · Cited by 19
Hu, D., Dong, R., Yang, Y., Chen, Z., Tang, Y. F., Fu, M., Wang, D. W., Xu, X., & Tu, L. (2019) · The FASEB Journal · doi:10.1096/fj.201802371rr · Cited by 19
“Once activated, receptorassociated Janus kinases (JAKs) and subsequent STAT transcription factors are phosphorylated and translocate to the nucleus to coordinate gene expressionbybinding to STAT-responsive gene elements (20).”
BackgroundNociceptor Overexpression of NaV1.7 Contributes to Chronic Muscle Pain Induced by Early-Life Stress
Álvarez, P., Bogen, O., Green, P. G., & Levine, J. D. (2021) · Journal of Pain · doi:10.1016/j.jpain.2021.02.003 · Cited by 19
NEK6 is an injury‐responsive kinase cooperating with STAT3 in regulation of reactive astrogliosis
Yu, Y., Shen, T., Zhong, X., Wang, L.-L., Tai, W., Zou, Y., Qin, J., Zhang, Z., & Zhang, C. (2021) · Glia · doi:10.1002/glia.24104 · Cited by 18
“Its transcriptional activity is regulated by cytokine-induced phosphorylation (Heinrich et al., 2003; Oliva et al., 2012; Sun et al., 2010; Truettner et al., 2005; Zhao et al., 2011).”
BackgroundYang, M., Yao, P., Lang, X., et al. (2021) · Bioengineered · doi:10.1080/21655979.2021.2001241 · Cited by 19
Napolitano, L., Orecchia, L., Giulioni, C., et al. (2022) · Applied Sciences · doi:10.3390/app13010275 · Cited by 19
Roles of Lipolytic enzymes in Mycobacterium tuberculosis pathogenesis
Lin, H., Xing, J., Wang, H., Wang, S., Ren, F., Li, X., Li, Z., & Song, N. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1329715 · Cited by 19
Fu, C. Y., Wang, L., & Cai, W. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1452849 · Cited by 24
Lipids and adipocytes involvement in tumor progression with a focus on obesity and diet
Calabrese, C., Miserocchi, G., Vita, A. D., Spadazzi, C., Cocchi, C., Vanni, S., Gabellone, S., Martinelli, G., Ranallo, N., Bongiovanni, A., et al. (2024) · Obesity Reviews · doi:10.1111/obr.13833 · Cited by 21
“106 MCP-1, also known as chemokine (C –”
Lee, H. K., Seo, I. A., Shin, Y. K., Park, J. W., Suh, D. J., & Park, H. T. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.03.046 · Cited by 19
Antoniu, S. A. (2009) · Biomarkers · doi:10.3109/13547500903311902 · Cited by 19
“IL-6 is also produced in the skeletal muscles and might be involved in inflammatory muscle wasting associated with COPD or in generation of pulmonary hypertension (Heinrich et al. 2003, Chaouat et al. 2009).”
BackgroundCross Talk between Peritoneal Macrophages and B-1 Cells In Vitro
Thies, F. G., Laurindo, M. F. L., Pérez, E. C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062805 · Cited by 19
“IL-6 is a cytokine produced by several cell types, including antigen presenting cells, such as macrophages and dendritic cells [29], and it induces B-cell proliferation [30].”
BackgroundLiu, T., Fei, Z., Gangavarapu, K. J., et al. (2013) · Leukemia Research · doi:10.1016/j.leukres.2013.06.026 · Cited by 19
“The gp130 forms a dimmer after the stimulation by IL-6 and leads to the activation of the Janusactivated kinase signal transducer and activator of transcription (STAT) signaling pathway [22, 38, 39].”
Clahsen, T., Lehmann, U., Stross, C., Hermanns, H., Volkmer‐Engert, R., Schneider-Mergener, J., Heinrich, P., & Schaper, F. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2004.09.016 · Cited by 20
Self-citationPartridge, M. A., Chai, Y., Zhou, H., et al. (2010) · International Journal of Radiation Biology · doi:10.3109/09553000903564034 · Cited by 19
“IL6 is a pro-inflammatory cytokine that is a critical regulator of the acute phase response to trauma, including radiation exposure (Choy and Panayi 2001; Dent et al. 2003; Heinrich et al. 2003).”
BackgroundEchevarría, F. D. (2013) · Journal of Clinical & Experimental Ophthalmology · doi:10.4172/2155-9570.1000286 · Cited by 19
“Once the entire signal complex is formed, gp130 is activated and initiates a variety of signal cascades that mediate transcription of pro- and anti- inflammatory factors [23-25].”
BackgroundTGF-B down regulates IL-6 signaling in intestinal epithelial cells: Critical role of SMAD-2
Walia, B., Wang, L., Merlin, D., & Sitaraman, S. V. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)81658-x · Cited by 19
CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice
Canup, B. S. B., Song, H., Ngo, V. L., Meng, X., Denning, T. L., Garg, P., & Laroui, H. (2016) · Digestive and Liver Disease · doi:10.1016/j.dld.2016.11.008 · Cited by 19
Characterization of type I interferon responses in dengue and severe dengue in children in Paraguay
Talarico, L. B., Byrne, A. B., Amarilla, S., et al. (2017) · Journal of Clinical Virology · doi:10.1016/j.jcv.2017.10.010 · Cited by 19
“IL-6 is secreted primarily by macrophages and lymphocytes in response to injury or infection [52] and, in concordance with our study, has been reported to be associated with the progression from mild dengue to severe forms of the disease [6-8, 53].”
ResultIL-5 in follicular fluid as a negative predictor of the intracytoplasmic sperm injection outcome
Alhilali, M. J. S., Parham, A., Attaranzadeh, A., Amirian, M., & Azizzadeh, M. (2018) · Cytokine · doi:10.1016/j.cyto.2018.07.016 · Cited by 20
Stephens, J. M., Bailey, J. L., Hang, H., Rittell, V., Dietrich, M. A., Mynatt, R. L., & Elks, C. M. (2018) · Obesity · doi:10.1002/oby.22254 · Cited by 19
“Oncostatin M (OSM), an adipokine belonging to the interleukin-6/ gp130 family of cytokines, regulates a variety of physiological and pathological processes (5,6).”
BackgroundMa, D., Wang, Y., Zhou, G., Wang, Y., & Li, X. (2019) · Inflammation · doi:10.1007/s10753-019-00959-6 · Cited by 19
Li, X., & Thirumalai, D. (2019) · Journal of The Royal Society Interface · doi:10.1098/rsif.2018.0820 · Cited by 18
“The producer (∆) cells secretes certain factors like Interleukin-6(IL-6) and/or Leukemia inhibitory factor (LIF), which enhance the proliferation and inhibit apoptosis of tumor cells [34, 65].”
BackgroundVilaiyuk, S., Lerkvaleekul, B., Soponkanaporn, S., Setthaudom, C., & Buranapraditkun, S. (2019) · Central European Journal of Immunology · doi:10.5114/ceji.2019.87066 · Cited by 16
“Binding of either complex to mgp130 induces homodimerisation and triggers a downstream signalling cascade [12, 13].”
BackgroundVendrell-Flotats, M., García‐Martínez, T., Martínez‐Rodero, I., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-74961-6 · Cited by 19
Overcoming Insulin Resistance with Ciliary Neurotrophic Factor
Allen, T. L., Matthews, V. B., & Febbraio, M. A. (2011) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-17214-4_9 · Cited by 20
“Adapted from Heinrich et al. (2003) Overcoming Insulin Resistance with Ciliary Neurotrophic Factor 185”
MethodShen, J., Jia, W., Yu, Y., Chen, J., Cao, X., Du, Y., Zhang, X., Zhu, S., Chen, W., Xi, J., et al. (2014) · Stem Cells · doi:10.1002/stem.1876 · Cited by 19
Poncet, N., Guillaume, J., & Mouchiroud, G. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2010.11.009 · Cited by 18
Rantala, A., Lajunen, T., Juvonen, R., Silvennoinen-Kassinen, S., Peitso, A., Vainio, O., Saikku, P., & Leinonen, M. (2011) · Human Immunology · doi:10.1016/j.humimm.2010.10.010 · Cited by 24
Increased cardiotrophin-1 in subjects with impaired glucose tolerance and newly diagnosed diabetes
Hung, H., Lu, F., Ou, H., et al. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.08.112 · Cited by 19
“Cardiotrophin-1 is onemember of the gp130 family of cytokines [1], and previous studies suggested that cardiotrophin-1 might be a potential marker of the development, progression, and regression of hypertensive heart disease [2].”
BackgroundKoutsouraki, E., Hatzifilippou, E., Michmizos, D., Cotsavasiloglou, C., Costa, V., & Balogiannis, S. (2011) · Journal of Neuropsychiatry · doi:10.1176/jnp.23.4.jnp442 · Cited by 18
Extracts fromDendropanax morbiferaLeaves Have Modulatory Effects on Neuroinflammation in Microglia
Shim, H.-J., Park, S., Lee, J., Park, H.-J., Baek, S., Kim, E. K., & Yu, S.-W. (2016) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x16500087 · Cited by 19
“NO, TNF-α, and IL-6 are the major pro-inflammatory cytokines produced by activated microglia during neuroinflammation (Carswell et al., 1975; Locksley et al., 2001; Heinrich et al., 2003; Park et al., 2011).”
BackgroundNelson, A. M., Katseff, A. S., Resnik, S. G., Ratliff, T. S., Zhu, A. S., & Garza, L. A. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2015.12.043 · Cited by 19
“Ciliary neurotrophic factor and leukemia inhibitory factor have also been linked to tissue regeneration, suggesting that the activity of gp130 is the critical key player in this pathway (Heinrich et al., 2003).”
BackgroundA PubMed-wide study of endometriosis
Liu, J., & Zhao, M. (2016) · Genomics · doi:10.1016/j.ygeno.2016.10.003 · Cited by 19
Hernández‐Caldera, A., Vernal, R., Paredes, R., et al. (2017) · International Endodontic Journal · doi:10.1111/iej.12872 · Cited by 19
Li, X., & Zhao, C. (2025) · Autoimmunity Reviews · doi:10.1016/j.autrev.2025.103826 · Cited by 21
Wang, T.-M., Hsieh, S., Chen, J., & Chiang, A.-N. (2013) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-013-1574-1 · Cited by 18
“STAT3 is an acute-phase response factor activated by phosphorylation at Tyr705, such activation leads to IL-6 regulation of many acute-phase protein genes [29].”
Cytokine-Induced JAK2-STAT3 Activates Tissue Regeneration under Systemic or Local Inflammation
Kim, Y. K., Lee, J. Y., & Suh, H. N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042262 · Cited by 18
“Those cytokines, IL-6 and TNFα, are crucial for tissue homeostasis maintenance through the JAK/STAT signaling pathway [22,23].”
BackgroundCao, D., Fan, Q., Li, Z., et al. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154201 · Cited by 18
Liu, C., Shi, L., Li, W., Huang, Z., Wang, S., Xu, P., Li, T., Li, Z., Luo, F., Li, W., et al. (2022) · Journal of Molecular Histology · doi:10.1007/s10735-022-10093-7 · Cited by 18
JAK-STAT signaling as an ARDS therapeutic target: Status and future trends
Zhang, Y., Gao, Z., Jiang, F., Yan, H., Yang, B., He, Q., Luo, P., Xu, Z., & Yang, X. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115382 · Cited by 18
Interleukin-11 Suppresses Ocular Surface Inflammation and Accelerates Wound Healing
Singh, A., Cho, W., Pulimamidi, V. K., et al. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.14.1 · Cited by 18
The preventive and inhibitory effects of red raspberries on cancer
Qi, Z., Yang, B., Giampieri, F., Cianciosi, D., Álvarez-Suárez, J. M., Elexpuru-Zabaleta, M., Quiles, J. L., Forbes-Hernández, T. Y., Zhang, D., Bai, W., et al. (2024) · Journal of Berry Research · doi:10.3233/jbr-240004 · Cited by 18
“Mitogen-activated protein kinases (MAPK) activation phosphorylates a variety of protein kinases that control cell proliferation, differentiation, migration, and cell death [48,49].”
Geethadevi, A., Ku, Z., Tsaih, S., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00593-y · Cited by 18
Gene transcription profile of the detached retina (An AOS Thesis).
Zacks, D. N. (2009) · PubMed Central · Cited by 18
The dynamics of the early inflammatory response in double-hit burn and sepsis animal models
Orman, M. A., Ierapetritou, M., Francois Berthiaume, B., & Androulakis, I. P. (2011) · Cytokine · doi:10.1016/j.cyto.2011.07.001 · Cited by 18
“IL-6 and IL-12 activate similar signaling cascades including JAK/STAT, and MAPK signaling pathways [50] [51] [52].”
Prieto, D. M. M., Ospina‐Prieto, S., Chaiwangyen, W., Weber, M., Hölters, S., Schleußner, E., Fitzgerald, J. S., & Markert, U. R. (2013) · The Scientific World JOURNAL · doi:10.1155/2013/259845 · Cited by 19
Neuropoietin activates STAT3 independent of LIFR activation in adipocytes
White, U. A., & Stephens, J. M. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.03.132 · Cited by 18
“It is also well established that gp130 cytokines induce the tyrosine phosphorylation of their recruited signal transducer receptors, including the LIFR, upon ligand binding (reviewed in [4].”
Backgroundvan Putte, B. P., Cobelens, P. M., van der Kaaij, N. P., et al. (2009) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2008.08.046 · Cited by 18
Circulating interleukin-6 and rheumatoid arthritis
Li, B., Xiao, Y. P., Xing, D., Ma, X., & Liu, J. (2016) · Medicine · doi:10.1097/md.0000000000003855 · Cited by 18
“functions in different pathophysiologic systems, including rheumatoid arthritis (RA).([1,2]) High concentrations of IL-6 in both the synovial fluid([3,4]) and serum of patients with RA suggested a”
BackgroundKang, Y., Yoon, S. B., & Park, B. (2018) · Oncology Reports · doi:10.3892/or.2018.6699 · Cited by 18
“Dilutions for primary antibodies used in the present study are as follows; MUC4 (1:1,000), p-Src (1:1,000), Src (1:1,000), XIAP (1:1,000), cleaved-caspase-3 (1:1,000), p-JAK1 (1:1,000), p-JAK2 (1:1,000), p-STAT1 (Y701, S727) (1:1,000), STAT1 (1:1,000), p-STAT3 (Y705) (1:1,000), p-FAK (1:1,000), FAK (1:1,000), JAK1 (1:…”
InfluentialThe role of oncostatin M receptor gene polymorphisms in bladder cancer
Deng, S., He, S. Y., Zhao, P., et al. (2019) · World Journal of Surgical Oncology · doi:10.1186/s12957-018-1555-7 · Cited by 18
GADD45a and GADD45b Genes in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients
Li, R., Lin, Y., Pan, Y., et al. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8060801 · Cited by 18
Shan, S., Zhou, Y. L., Yu, J., Yang, Q., Pan, D., Wang, Y., Li, L., Zhu, J.-Z., Zhang, Y. L., Huang, S., et al. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.105914 · Cited by 18
Gabrielyan, A., Quade, M., Gelinsky, M., & Rösen‐Wolff, A. (2020) · Stem Cell Research · doi:10.1016/j.scr.2020.101814 · Cited by 18
Aarstad, H. H., Moe, S. E., Bruserud, Ø., Lybak, S., Aarstad, H. J., & Tvedt, T. H. A. (2020) · Biomedicines · doi:10.3390/biomedicines8100418 · Cited by 18
“First, the main downstream pathway for the IL6 family/gp130 is JAK-STAT3, but the Mitogen-activated protein kinases (MAPK)/ERK and the PI3K-Akt-mammalian target of rapamycin (mTOR) pathways are also activated [64,65].”
Background
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
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