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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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Th17 Differentiation and Their Pro-inflammation Function
Song, X., Gao, H., & Qian, Y. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-94-017-9487-9_5 · Cited by 70
“IL-6 binds to its receptor complex IL-6Rα and gp130 to activate STAT1 and STAT3 for downstream biological activities [94].”
BackgroundKrzemień, J., Crozatier, M., & Vincent, A. (2010) · The International Journal of Developmental Biology · doi:10.1387/ijdb.093053jk · Cited by 77
Lin, C.-M., Shyu, K., Wang, B.-W., et al. (2010) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf100421w · Cited by 69
Dumoutier, L., de Meester, C., Tavernier, J. H., & Renauld, J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.007955 · Cited by 72
de Matos, D. G., Miller, K. A., Scott, R., et al. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.10.061 · Cited by 69
Green tea catechins inhibit angiogenesis through suppression of STAT3 activation
Leong, H., Mathur, P., & Greene, G. L. (2008) · Breast Cancer Research and Treatment · doi:10.1007/s10549-008-0196-x · Cited by 70
“with a family of inhibitory factors known as protein inhibitors of activated STAT (PIAS), and feedback inhibition by suppressor of cytokine signaling (SOCS) proteins [21, 35, 36].”
BackgroundSignaling network of Oncostatin M pathway
Dey, G., Radhakrishnan, A., Syed, N., Thomas, J. K., Nadig, A., Srikumar, K., Mathur, P. P., Pandey, A., Lin, S., Raju, R., et al. (2012) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-012-0186-y · Cited by 69
“Oncostatin M (OSM), belonging to the IL-6 family of cytokines (Heinrich et al. 2003), was first reported and purified from U937 monocytic cells (Zarling et al.”
BackgroundCaffarel, M. M., Chattopadhyay, A., Araujo, A. M., et al. (2013) · The Journal of Pathology · doi:10.1002/path.4222 · Cited by 69
“OSM is a member of the IL-6 cytokine family, and is known to signal through JAK–STAT pathways to activate context-dependent target genes [27].”
BackgroundLacroix, M., Rousseau, F., Guilhot, F., Malinge, P., Magistrelli, G., Herren, S., Jones, S. A., Jones, G. W., Scheller, J., Lissilaa, R., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.682138 · Cited by 70
“Upon IL-6 binding, mbIL-6R or sIL-6R recruits the ubiquitously expressed membrane protein gp130 that when dimerized activates JAK/STAT intracellular signaling pathways (5).”
BackgroundTOPICAL p38MAPK INHIBITION REDUCES DERMAL INFLAMMATION AND EPITHELIAL APOPTOSIS IN BURN WOUNDS
Ipaktchi, K. R., Mattar, A., Niederbichler, A. D., et al. (2006) · Shock · doi:10.1097/01.shk.0000225739.13796.f2 · Cited by 69
“These results are corroborated in part by the finding that MAPKAP-2 has been shown to stabilize IL-6 mRNA, leading to greater cytokine translation (29).”
ResultAcute myotube protein synthesis regulation by IL-6-related cytokines
Gao, S., Durstine, J. L., Koh, H.-J., Carver, W. E., Frizzell, N., & Carson, J. A. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00112.2017 · Cited by 69
“The binding of the IL-6 family of cytokines on the receptor complex containing its specific receptor and gp130 causes the phosphorylation of gp130 intracellular tyrosine residues and STAT3 by the Janus kinases JAK1 and JAK2 (22).”
BackgroundInfluentialCytokine storm in tuberculosis and IL-6 involvement
Boni, F. G., Hamdi, I., Koundi, L. M., Shrestha, K., & Xie, J. (2021) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2021.105166 · Cited by 68
Levy, G., Guglielmelli, P., Langmuir, P. B., & Constantinescu, S. N. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002838 · Cited by 70
Epidermal loss of JunB leads to a SLE phenotype due to hyper IL-6 signaling
Pflegerl, P., Vesely, P. W., Hantusch, B., Schlederer, M., Zenz, R., Janig, E., Steiner, G., Meixner, A., Petzelbauer, P., Wolf, P., et al. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0910371106 · Cited by 70
“The strong expression of Socs proteins change global phosphotyrosine-dependent signaling, since Socs proteins target phosphotyrosine proteins, such as kinases to the proteasome (2).”
BackgroundDemyanets, S., Kaun, C., Rychli, K., Pfaffenberger, S., Kastl, S., Hohensinner, P. J., Rega‐Kaun, G., Katsaros, K. M., Afonyushkin, T., Bochkov, V. N., et al. (2010) · Basic Research in Cardiology · doi:10.1007/s00395-010-0141-0 · Cited by 68
Macciò, A., & Madeddu, C. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1080-7 · Cited by 70
“The efficient induction of the IL-6 promoter requires the interaction of several transcription factors, including the CCAAT/enhancer-binding protein (C/EBP) family members, and nuclear factor (NF)-kB, which interact with each other to synergistically upregulate the IL-6 promoter, whereas p53 and the retinoblastoma gen…”
BackgroundBall, S. L., Li, C., Li, P., & Lin, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018820 · Cited by 70
“The binding of IL-6 to its receptor leads to the activation of the Janus kinase family which in turn phosphorylate STAT3 [38].”
BackgroundHernández‐Quintero, M., Kuri‐Harcuch, W., Robles, A. G., & Castro‐Muñozledo, F. (2006) · Cell and Tissue Research · doi:10.1007/s00441-006-0173-9 · Cited by 68
“Since IL-6 activates signal transduction pathways (Heinrich et al. 2003) different from those activated by EGF (Jorissen et al. 2003), cytoskeletal aggregation might be attributable to differences in keratin phosphorylation or changes in keratin association with IFAPs.”
BackgroundSong, H., & Lim, H. J. (2006) · Reproduction · doi:10.1530/rep.1.00956 · Cited by 68
“OSM, CNTF, and CT-1 also use LIFR as part of their high affinity receptor complex (Heinrich et al. 2003).”
BackgroundGünther, J., Petzl, W., Zerbe, H., Schuberth, H., Koczan, D., Goetze, L., & Seyfert, H. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-17 · Cited by 69
“These three factors together orchestrate and dominate many aspects of the local as well as systemic immune response [42,43].”
BackgroundSuppression of inflammatory and immune responses by the A2Aadenosine receptor: an introduction
Palmer, T. M., & Trevethick, M. A. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707524 · Cited by 71
“induction, the SH2 domain binds to specific phosphor-Tyr residues present on target cytokine receptors, such as gp130 and the leptin receptor Ob-R (Heinrich et al., 2003) (Figure 1).”
BackgroundChang, K.-T., Tsai, C., Chiou, Y.-C., Chiu, C., Jeng, K.-S., & Huang, C. F. (2005) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00089.2005 · Cited by 68
“Interleukin-6 (IL-6), a cytokine initially recognized as a regulator of immune and inflammatory responses, is also a growth modulator of many tumor cells (11, 18).”
BackgroundWinslow, S., Odqvist, L., Diver, S. E., Riise, R. E., Abdillahi, S. M., Wingren, C., Lindmark, H., Wellner, A., Lundin, S., Yrlid, L., et al. (2021) · European Respiratory Journal · doi:10.1183/13993003.03312-2020 · Cited by 67
An Overview of Glycosylation and its Impact on Cardiovascular Health and Disease
Loaeza-Reyes, K. J., Zenteno, E., Rodríguez, A. M., Rosas, R. T., Argueta‐Figueroa, L., Salinas-Marín, R., Castillo-Real, L. M., Pina-Canseco, M. D. S., & Pérez-Cervera, Y. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.751637 · Cited by 70
“, 2004), which impairs the action of this hormone by binding with the IRS-1 and IRS-2, inducing the ubiquitination and degradation of the latter, leading to insulin resistance (Heinrich et al., 2003), a state of hyperglycemia with subsequent compensatory hyperinsulinemia, followed by wasting and claudication and apopt…”
BackgroundSharma, T., Gupta, A., Chauhan, R., Bhat, A. A., Nisar, S., Hashem, S., Akhtar, S., Ahmad, A., Haris, M., Singh, M., et al. (2022) · Cancer and Metastasis Reviews · doi:10.1007/s10555-022-10026-6 · Cited by 71
“The cytokine, IL-6 signals by associating its receptor (IL-6Rα) with gp130 and induces downstream recruitment and activation of several molecules (SHP2, Ras-mitogen-activated protein kinase, and phosphatidylinositol 3 kinase) and the STAT1 and STAT3 transcription factors [111].”
BackgroundThe Role of Inflammation in Inflammatory Breast Cancer
Fouad, T. M., Kogawa, T., Reuben, J. M., & Ueno, N. T. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-0348-0837-8_3 · Cited by 68
“In turn, IL-6 activates multiple effectors involved in the process of invasion and metastasis (Heinrich et al. 2003; Tawara et al. 2011).”
BackgroundResultDuval, D., Malaisé, M., Reinhardt, B., Kédinger, C., & Bœuf, H. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401337 · Cited by 66
Signaling networks in hepatic oval cell activation
Erker, L. R., & Grompe, M. (2008) · Stem Cell Research · doi:10.1016/j.scr.2008.01.002 · Cited by 67
Molecular mechanisms of peripheral nerve regeneration: emerging roles of microRNAs
Wu, D., & Murashov, A. K. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00055 · Cited by 72
“Injury induced IL-6 activates the phosphorylation of STAT3, and the expression of a set of responsive genes (Heinrich et al., 2003).”
Adipose expression of adipocytokines in women with polycystic ovary syndrome
Svendsen, P. F., Christiansen, M., Hedley, P. L., Nilas, L., Pedersen, S. B., & Madsbad, S. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.03.056 · Cited by 67
Diet-derived polyphenols inhibit angiogenesis by modulating the interleukin-6/STAT3 pathway
Lamy, S., Akla, N., Ouanouki, A., Lord‐Dufour, S., & Béliveau, R. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.04.004 · Cited by 68
“To further investigate the cellular mechanisms involved in the inhibition of migration and growth by polyphenols, we next explored the potential involvement of two major signaling pathways: the JAK/STAT3 pathway and the MAPK pathway, both being involved in IL-6mediated functions in several cell types [12].”
Pelosi, M., Rossi, M. D., Barberi, L., & Musarò, A. (2014) · BioMed Research International · doi:10.1155/2014/206026 · Cited by 67
“IL-6-induced Stat signaling also initiates a negative feedback regulation through the increased transcription of the suppressor of cytokine signaling (SOCS) proteins [27].”
BackgroundMicroarray and Proteomic Analysis of Breast Cancer Cell and Osteoblast Co-cultures
Morrison, C., Mancini, S., Cipollone, J., Kappelhoff, R., Roskelley, C. D., & Overall, C. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.222513 · Cited by 67
The biology behind interleukin-6 targeted interventions
Liu, X., Jones, G. W., Choy, E., & Jones, S. A. (2016) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000255 · Cited by 52
Gao, J., Zhao, S., & Halstensen, T. (2016) · Oncology Report · doi:10.3892/or.2016.4765 · Cited by 69
“In addition, IL-6 initiates the PI3K/AKT and RAS/RAF/MEK/ERK pathways, which regulate cell proliferation (5).”
BackgroundZhu, X., Shen, H., Yin, X., Long, L., Chen, X., Feng, F., Liu, Y., Zhao, P., Xu, Y., Li, M., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.16610 · Cited by 67
“This binding leads to the recruitment of the signal transducing subunit gp130 and subsequently activates signal transducer and activator of transcription 3 (STAT3) [14, 15], which is the most common member of the STAT protein family and consistently constitutively activated in cancers.”
BackgroundInvolvement of the myeloid cell compartment in fibrogenesis and systemic sclerosis
Kania, G., Rudnik, M., & Distler, O. (2019) · Nature Reviews Rheumatology · doi:10.1038/s41584-019-0212-z · Cited by 66
Transcriptional Regulation of the Human μ-Opioid Receptor Gene by Interleukin-6
Börner, C., Kraus, J., Schröder, H., Ammer, H., & Höllt, V. (2004) · Molecular Pharmacology · doi:10.1124/mol.104.003806 · Cited by 66
Atzeni, F., Nucera, V., Masala, I. F., Sarzi‐Puttini, P., & Bonitta, G. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104402 · Cited by 66
Li, R., Fang, H., Shen, J., et al. (2021) · Toxins · doi:10.3390/toxins13030208 · Cited by 66
The immunopathogenesis of sarcoidosis
Miedema, J., Cinetto, F., Smed‐Sörensen, A., & Spagnolo, P. (2024) · Journal of Autoimmunity · doi:10.1016/j.jaut.2024.103247 · Cited by 76
Altered bone development and turnover in transgenic mice over‐expressing Lipocalin‐2 in bone
Costa, D., Lazzarini, E., Canciani, B., Giuliani, A., Spanò, R., Marozzi, K., Mănescu, A., Cancedda, R., & Tavella, S. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24391 · Cited by 66
“The trabecular structure inside the femur was imaged in three dimensions to obtain 3D quantitative parameters of trabecular bone architecture by the VG Studio Max commercial software (Hildebrand and Ruegsegger, 1997).”
MethodBélanger, M., Allaman, I., & Magistretti, P. J. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07135.x · Cited by 71
Crif1 is a novel transcriptional coactivator of STAT3
Kwon, M. C., Koo, B., Moon, J.-S., Kim, Y. Y., Park, K. C., Kim, N.-S., Kwon, M. Y., Kong, M.-P., Yoon, K., Im, S.-K., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601986 · Cited by 65
“Significant progress has been made in the elucidation of the positive and negative regulation of STAT3 signalling (Levy and Darnell, 2002; Heinrich et al, 2003).”
BackgroundVardam, T. D., Zhou, L., Appenheimer, M. M., Chen, Q., Wang, W.-C., Baumann, H., & Evans, S. S. (2007) · Cytokine · doi:10.1016/j.cyto.2007.07.184 · Cited by 67
“IL-6 signal transduction can occur through a complex consisting of membrane-anchored IL-6Rα and gp130 via a mechanism termed classical signaling (Figure 1) [34,35].”
BackgroundInfluentialmicroRNAs as Regulators of Adipogenic Differentiation of Mesenchymal Stem Cells
Hamam, D., Ali, D., Kassem, M. S., Aldahmash, A. M., & Alajez, N. M. (2014) · Stem Cells and Development · doi:10.1089/scd.2014.0331 · Cited by 68
“Leukemia inhibitory factor (LIF) is an inflammatory cytokine that plays a significant role in regulating multiple biological activities such as cell survival, proliferation, and cell differentiation [51].”
BackgroundAgorastos, A., Hauger, R. L., Barkauskas, D. A., Moeller‐Bertram, T., Clopton, P., Haji, U., Lohr, J. B., Geracioti, T. D., Patel, P. M., Chrousos, G. P., et al. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.02.020 · Cited by 65
“The pleiotropic biology of IL-6 is mediated through a number of different signal transduction pathways (Heinrich et al., 2003; Rose-John and Heinrich, 1994).”
BackgroundWu, D., Yang, M., Chen, Y., Jia, Y., Ma, Z. A., Boden, G. H., Li, L., & Yang, G. (2014) · Diabetes · doi:10.2337/db13-0899 · Cited by 65
Bluyssen, H. A. R., Rastmanesh, M. M., Tilburgs, C., Jie, K. E., Wesseling, S., Goumans, M., de Boer, P., Joles, J. A., & Braam, B. G. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00513.2009 · Cited by 66
“Upon binding to their cognate receptors, IFN and IL-6 activate Jak1 and Jak2 from the Janus kinase family (11, 33), which terminate in activation of signal transducer and activator of transcription (STAT)1 and STAT3 in different cell types (2, 16).”
BackgroundDeleterious effect of triple antibiotic paste on human periodontal ligament fibroblasts
Yadlapati, M., de Souza, L. C., Dorn, S. O., et al. (2013) · International Endodontic Journal · doi:10.1111/iej.12216 · Cited by 66
Grossberg, A. J., Scarlett, J. M., Zhu, X., Bowe, D. D., Batra, A. K., Braun, T. P., & Marks, D. L. (2009) · Endocrinology · doi:10.1210/en.2009-1135 · Cited by 66
“tion of the Janus kinase 2/signal transducer and activator of transcription (STAT3) pathway (38), the same pathway activated by the binding of leptin to its receptor (39).”
BackgroundMahdavi, A., Davey, R. E., Bhola, P., Yin, T., & Zandstra, P. W. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030130 · Cited by 65
“In this model, we assumed pre-association of Jak with the receptors according to literature [21,22], and we have assumed reversible kinetics as shown by double arrows in Figure 1 [20].”
MethodCalprotectin is released from human skeletal muscle tissue during exercise
Mortensen, O. H., Andersen, K., Fischer, C. P., Nielsen, A. R., Nielsen, S. J., Akerstrom, T. C. A., Aastrøm, M., Borup, R., & Pedersen, B. K. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.153551 · Cited by 66
“Furthermore, binding of IL-6 to its receptor leads to an activation of the MAPK and PI3K pathways (Heinrich et al. 2003).”
BackgroundIL-6 and ICOS Antagonize Bim and Promote Regulatory T Cell Accrual with Age
Raynor, J. L., Karns, R. A., Almanan, M., Li, K., Divanovic, S., Chougnet, C. A., & Hildeman, D. A. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500443 · Cited by 67
“IL-6 can induce ERK activation (62), and thus may enhance TCR/CD28-driven ICOS expression on Tregs through”
BackgroundCastleman's disease—a two compartment model of HHV8 infection
Schulte, K., & Talat, N. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.103 · Cited by 63
“Alternatively, IL-6 activates the mitogen-activated protein kinase (MAPK) cascade”
BackgroundHenkel, J., Gärtner, D., Dorn, C., Hellerbrand, C., Schanze, N., Elz, S. R., & Püschel, G. P. (2011) · Laboratory Investigation · doi:10.1038/labinvest.2011.47 · Cited by 65
“OSM belongs to the class of cytokines that use the common receptor subunit gp130 for signal transduction that activates the JAKsSTAT pathway”
BackgroundAnalysis of the Foxp3/Scurfin Gene in Crohn's Disease
Park, O., Grishina, I., Leung, P. S. C., Gershwin, M. E., & Prindiville, T. P. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1361.125 · Cited by 65
Deng, W., Cheung, D. S. T., Tsao, S. W., Wang, X. M., & Tiwari, A. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.11.017 · Cited by 66
Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise
Barcelos, R. P., Royes, L. F. F., González‐Gallego, J., & Bresciani, G. (2017) · Free Radical Research · doi:10.1080/10715762.2017.1291942 · Cited by 66
“and the upregulation of suppressor of cytokine signaling (SOCS)-3 [119], which are, together with”
BackgroundNeal, E. G., Acosta, S. A., Kaneko, Y., Ji, X., & Borlongan, C. V. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18766172 · Cited by 65
Kino, T., Rice, K. C., & Chrousos, G. P. (2007) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2007.01796.x · Cited by 67
Robustness and Information Transfer within IL-6-induced JAK/STAT Signalling
Billing, U., Jetka, T., Nortmann, L., Wundrack, N., Komorowski, M., Waldherr, S., Schaper, F., & Dittrich, A. (2019) · Communications Biology · doi:10.1038/s42003-018-0259-4 · Cited by 64
Self-citationOsteoblast/osteocyte-derived interleukin-11 regulates osteogenesis and systemic adipogenesis
Dong, B., Hiasa, M., Higa, Y., Ohnishi, Y., Endo, I., Kondo, T., Takashi, Y., Tsoumpra, M. K., Kainuma, R., Sawatsubashi, S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34869-3 · Cited by 65
JAK-STAT signaling in hepatic fibrosis
Mair, M. (2011) · Frontiers in bioscience · doi:10.2741/3886 · Cited by 64
“STAT3 The cytokine IL-6 activates STAT3 and the mitogen-activated protein kinase (MAPK) signaling pathway through the gp130–IL-6R complex (57).”
BackgroundTherapeutic targeting of the oncostatin M receptor-β prevents inflammatory heart failure
Pöling, J., Gajawada, P., Richter, M., et al. (2013) · Basic Research in Cardiology · doi:10.1007/s00395-013-0396-3 · Cited by 64
“It seems likely that inhibition of Ob reduced activity of gp130 only partially, since gp130 can also act as a homodimer and heterodimerize with other receptors [12].”
BackgroundChollangi, S., Wang, J., Martin, A. J., Quinn, J. P., & Ash, J. D. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.03.012 · Cited by 66
Cantharidin induces apoptosis of human multiple myeloma cells via inhibition of the JAK/STAT pathway
Sagawa, M., Nakazato, T., Uchida, H., Ikeda, Y., & Kizaki, M. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.00872.x · Cited by 65
McNamee, E. N., Ryan, K. M., Griffin, É. W., González-Reyes, R. E., Ryan, K. J., Harkin, A., & Connor, T. J. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.02.005 · Cited by 64
Quarta, S., Baeumer, B. E., Scherbakov, N., Andratsch, M., Rose‐John, S., Dechant, G., Bandtlow, C. E., & Kress, M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1209-13.2014 · Cited by 65
“Neuropoietic cytokines bind to membrane-bound or soluble receptors as factor-specific receptor subunits (Heinrich et al., 2003; Jones et al., 2011).”
BackgroundInfluentialSanto, L., Hideshima, T., Cirstea, D., Bandi, M., Nelson, E., Gorgun, G., Rodig, S., Vallet, S., Pozzi, S., Patel, K., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-3012 · Cited by 61
“JAKs are cytoplasmatic protein tyrosine kinases that are constitutively associated with several cytokines; IL-6 induces gp130 (IL-6 receptor) dimerization, thereby resulting in the autophosphorylation of JAK and activation of various signaling transducers and activators of transcription (STAT) proteins (14) (15).”
Yen, C., Liao, S., Huang, S.-T. J., Tabak, S., Arcuri, F., Lee, C., Arici, A. M., Petraglia, F., Wang, H., & Kayisli, U. A. (2016) · Reproductive Sciences · doi:10.1177/1933719116681515 · Cited by 65
Liu, Y., Deng, S., Zhang, Z., Gu, Y., Xia, S., Bao, X., Cao, X., & Xu, Y. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173294 · Cited by 65
Goralski, K. B., & Sinal, C. J. (2007) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y06-092 · Cited by 66
“IL-6 exerts its actions through the IL-6 receptor, which is composed of a single transduction subunit (GP130) and an IL-6 binding subunit (Heinrich et al. 2003).”
BackgroundNg, I. H. W., Ng, D. C. H., Jans, D. A., & Bogoyevitch, M. A. (2012) · Biochemical Journal · doi:10.1042/bj20120941 · Cited by 63
“TheIL-6family ofcytokines,whichincludesOSM(oncostatinM)andLIF (leukaemiainhibitoryfactor),signalsthroughthecommon gp130(glycoprotein130)receptorchaintoactivateSTAT3 [4].”
IL-6 and its role in IgA nephropathy development
Groza, Y., Jemelková, J., Kafkova, L. R., Malý, P., & Raška, M. (2022) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2022.04.001 · Cited by 67
Li, Q., Wang, L., Tan, W., Peng, Z. J., Luo, Y., Zhang, Y., Zhang, G., Na, D., Jin, P., Shi, T., et al. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.05.005 · Cited by 65
“[24–26].”
Floss, D. M., Mrotzek, S. M., Klöcker, T., Schröder, J., Grötzinger, J., Rose‐John, S., & Scheller, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.432153 · Cited by 64
“IL-6-gp130STAT3 activation is rapidly switched off by SOCS3-negative feedback regulation (47).”
BackgroundLeptin Signaling: A Key Pathway in Immune Responses
Procaccini, C., Lourenço, E. V., Matarese, G., & Cava, A. L. (2009) · Current Signal Transduction Therapy · doi:10.2174/157436209787048711 · Cited by 64
“Jabado N, Jauliac S, Pallier A, Bernard F, Fischer A, Hivroz C. Sam68 association with p120GAP in CD4+ T cells is dependent on CD4 molecule expression.”
BackgroundInfluentialRoles of STATs signaling in cardiovascular diseases
Kishore, R., & Verma, S. (2012) · JAK-STAT · doi:10.4161/jkst.20115 · Cited by 62
“Another negative feedback mechanism of the JAK/STAT pathway comprises SHP-2 proteins (src homology 2 domain containing protein tyrosine phosphatase), which dephosphorylate the receptor, JAK or STAT proteins.(21) The details of the canonical JAK-STAT signaling pathway have been extensively reviewed elsewhere.”
BackgroundKarakhanova, S., Meisel, S., Ring, S., Mahnke, K., & Enk, A. (2009) · European Journal of Immunology · doi:10.1002/eji.200939289 · Cited by 62
Haan, C., Behrmann, I., & Haan, S. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01018.x · Cited by 64
“Alternatively, a non-structured cytoplasmic tail of a cytokine receptor would have to adopt a loop structure, which would require to wind repeatedly through the clefts or along the surface of the FERM domain [7, 63].”
BackgroundSelf-citationGene network and canonical pathway analysis in prostate cancer: a microarray study
Savlı, H., Szendrői, A., Romics, I., & Nagy, B. (2008) · Experimental & Molecular Medicine · doi:10.3858/emm.2008.40.2.176 · Cited by 63
“Dysregulation of IL-6-type cytokine signaling was reported to contribute to PCA previously (Heinrich et al., 2003).”
BackgroundGoren, I., Kämpfer, H., Müller, E., Schiefelbein, D., Pfeilschifter, J. M., & Frank, S. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700136 · Cited by 63
Lou, Y., He, T., Jiang, F., Shi, J., & Zhu, J. (2014) · Talanta · doi:10.1016/j.talanta.2014.01.016 · Cited by 63
Acute and long‐term effects of IL‐6 on cultured dorsal root ganglion neurones from adult rat
von Banchet, G. S., Kiehl, M. M. D., & Schaible, H. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03185.x · Cited by 66
Gorina, R., Petegnief, V., Chamorro, Á., & Planas, A. M. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02878.x · Cited by 63
“Anchorage of Jak1 to gp130 triggers Tyr phosphorylation of the kinase (Haan et al. 2002) and this activation is essential for the subsequent IL-6-induced signalling process (Guschin et al. 1995; Rodig et al. 1998; Heinrich et al. 2003).”
BackgroundAdipose tissue insulin action and IL-6 signaling after exercise in obese mice
MACPHERSON, R. E. K., HUBER, J. S., FRENDO-CUMBO, S., SIMPSON, J. A., & WRIGHT, D. C. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000660 · Cited by 62
Tawara, K., Scott, H., Emathinger, J. M., Ide, A. E., Fox, R., Greiner, D., LaJoie, D., Hedeen, D. S., Nandakumar, M., Oler, A. J., et al. (2018) · Translational Oncology · doi:10.1016/j.tranon.2018.10.004 · Cited by 63
“This may be caused by the fact that OSM, IL-6, and their receptors are associated with increased metastatic capacity [57,58], including increased invasion and migration [20,24,25,29,59] and the promotion of angiogenesis [26,27,31,60].”
Tsimberidou, A. M., Vining, D. J., Arora, S. P., de Achaval, S., Larson, J., Kauh, J. S. W., Cartwright, C., Avritscher, R., Alibhai, I. N., Tweardy, D. J., et al. (2025) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-2920 · Cited by 67
“20–23 ), and Src kinases ( e. g. TTI-101 has been shown to have limited toxicity in laboratory animals in Good Laboratory Practice toxicology studies.”
Moreira, D., Zhang, Q., Hossain, D. M. S., Nechaev, S., Li, H., Kowolik, C. M., D’Apuzzo, M., Forman, S. J., Jones, J. O., Pal, S. K., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4029 · Cited by 62
“IL-6 is known for inducing rapid STAT3 phosphorylation through the IL-6R-associated Janus family kinases (JAKs) [36].”
BackgroundWang, G., Qian, P., Jackson, F. R., Qian, G., & Wu, G. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.08.008 · Cited by 63
“To define if the IL6-JAK-STAT pathway was involved in the activation of XDH/XO, we determined the effect of IL-6 antibodies and the JAK2 inhibitor AG490 on the XDH/XO activation.”
BackgroundInfluentialGenome-wide Association Studies for Osteoporosis: A 2013 Update
Liu, Y., Zhang, L., Papasian, C. J., & Deng, H. (2014) · Journal of Bone Metabolism · doi:10.11005/jbm.2014.21.2.99 · Cited by 62
“Protein post-translational modifications, such as protein phosphorylation, have also been shown to play significant roles in regulating gene expression,[60,61] signal transduction,[62,63] and cellular functions[64] closely related to bone metabolism.”
BackgroundMolecular aspects of medicine: from experimental to clinical hepatology
Häussinger, D. (2004) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2004.02.001 · Cited by 62
Kühn, M. C., Willenberg, H. S., Schott, M., Papewalis, C., Stumpf, U. C., Flohé, S., Scherbaum, W. A., & Schinner, S. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.10.018 · Cited by 62
“, 2008) using JAK for intracellular signal transduction (Bellido et al., 1997; Heinrich et al., 2003).”
MethodMeads, M. B., & Medveczky, P. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407382200 · Cited by 62
Isomoto, H. (2009) · Digestion · doi:10.1159/000167859 · Cited by 62
Cytokine signalling via gp130 in gastric cancer
Howlett, M., Menheniott, T. R., Judd, L. M., & Giraud, A. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2009.07.009 · Cited by 65
Mitogen Activated Protein kinase signal transduction pathways in the prostate
MARONI, P. D., Koul, S., Meacham, R. B., et al. (2004) · Cell Communication and Signaling · doi:10.1186/1478-811x-2-5 · Cited by 62
“The JAK/STAT family of proteins also appears to be able to activate p38 MAP kinase [12].”
InfluentialIntracellular signalling during female gametogenesis
Sobinoff, A. P., Sutherland, J. M., & McLaughlin, E. A. (2012) · Molecular Human Reproduction · doi:10.1093/molehr/gas065 · Cited by 65
“Therefore, Clc may contribute to primordial follicle activation, interacting with Socs4 in a negative feedback loop (Heinrich et al., 2003; Katoh, 2007; Croker et al., 2008).”
BackgroundOjo, D., Lin, X., Wong, N., Gu, Y. J., & Tang, D. (2015) · Cancers · doi:10.3390/cancers7040890 · Cited by 64
“IL-6 has a key role in systemic inflammation via binding to the IL-6-receptor/gp130 complex, which leads to JAK-derived phosphorylation of STAT3 at tyrosine (Tyr) 705 (pSTAT3) and consequently pSTAT3-mediated transactivation of target genes [94,95].”
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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