Principles of interleukin (IL)-6-type cytokine signalling and its regulation

In the paper

“Human OSM has the exceptional capability to recruit two different receptor complexes.It forms both LIFR-gp130 and OSMR-gp130 heterodimers.”

What the sources say

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  cites [4]
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  cites [6]

In the paper

“LIF and OSM directly engage their signalling receptor subunits without requirement for additional α-receptor subunits (Figure 2) [4,6].”

What the sources say

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  cites [4]
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  cites [6]

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].”

What the sources say

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  cites [4]

In the paper

“It has been demonstrated that sIL-6Rα potentiates the antagonistic activity of sgp130.”

What the sources say

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  cites [7]

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].”

What the sources say

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  cites [17]
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  cites [18]

In the paper

“The minimal requirement for receptor activation is one intact antibody and the Fab (fragment antigen binding) of the second antibody.”

What the sources say

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  cites [39]
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  cites [40]

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].”

What the sources say

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  cites [36]
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  cites [37]

In the paper

“Thus in the homodimer two different binding epitopes of gp130 are involved in ligand recognition [23].”

What the sources say

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  cites [23]

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].”

What the sources say

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  cites [24]

In the paper

“In contrast with the α-receptors, the receptors that initiate signal transduction have three additional membrane-proximal FNIII domains [4].”

What the sources say

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  cites [4]

In the paper

“To become secreted, CLC must be coexpressed with either CLF-1 (cytokine-like factor-1) or CNTFRα.”

What the sources say

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  cites [12]
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  cites [13]

In the paper

“A surprise was the discovery that site III is recognized by the Ig-like domain of gp130, LIFR or OSMR [19][20][21][22].”

What the sources say

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  cites [19]
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  cites [20]
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  cites [21]
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  cites [22]

In the paper

“Interestingly, insertion of one to four alanine residues into the membrane-proximal intracellular region of gp130 demonstrated that full activation of the receptor (i.e.induction of target genes) was only obtained with the wild-type and the + 3A-mutant [45].”

What the sources say

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  cites [45]

In the paper

“Unlike many other receptors, efficient gp130 activation could not be achieved by a single antibody, but requires the action of two distinct monoclonal antibodies [39,40].”

What the sources say

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  cites [39]
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  cites [40]

In the paper

“it contains a tyrosine-based and a dileucine-type motif which direct sorting of IL-6Rα to the basolateral membrane of polarized cells.”

What the sources say

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  cites [8]

In the paper

“An independent study on the EpoR (erythropoietin receptor) juxtamembrane intracellular region also described an α-helical dependency of Epo-induced signal transduction [46].”

What the sources say

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  cites [46]

In the paper

“stimulation of fibrosarcoma cells with OSM leads to a pronounced phosphorylation of the IFN (interferon) receptor chain 1 [33]”

What the sources say

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  cites [33]

In the paper

“in murine embryonic fibroblasts lacking the IFNα-IFNβ signalling complex IL-6 signals are significantly reduced [34].”

What the sources say

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  cites [34]

In the paper

“The signal transducing chains gp130, LIFR and OSMR bind to JAK1, JAK2 and TYK2 [47][48][49][50].”

What the sources say

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  cites [47]
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  cites [48]
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  cites [49]
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  cites [50]

In the paper

“Indeed, in gp130 [26] and the LIFR [27] dileucine-like motifs have been identified that are required for receptor-mediated ligand internalization.”

What the sources say

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  cites [26]
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  cites [27]

In the paper

“Thus the naturally occuring combination of sIL-6Rα and sgp130 might act as a kind of buffer to modulate systemic responses to circulating IL-6 [7].”

What the sources say

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  cites [7]

In the paper

“A domain model of the IL-6 receptor complex [36], as well as the recent X-ray data [24], show that the C-termini of the two CBMs in the gp130 homodimer are separated by a distance of about 9 nm.”

What the sources say

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  cites [36]
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  cites [24]

In the paper

“STAT1 is recruited to the more restricted consensus sequence pYXPQ (Y 905 LPQ and Y 915 MPQ in gp130) [84].”

What the sources say

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  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [84]

In the paper

“In the case of STAT3 activation after IL-6 stimulation of HepG2 cells, two distinct pathways for the serine phosphorylation have been identified: one sensitive and the other insensitive to the serine/threonine kinase inhibitor H7 [98].”

What the sources say

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  cites [98]

In the paper

“In prolactin-stimulated mammary epithelial cells serine phosphorylation has an impact on signal duration [101].”

What the sources say

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  cites [101]

In the paper

“Deletion of the proline-rich box1 or mutation of two critical proline residues within box1 abrogates receptor binding of JAKs to gp130, OSMR or LIFR [49,53,54].”

What the sources say

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  cites [49]
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  cites [53]
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  cites [54]

In the paper

“Co-expression of JAK1, JAK2 and TYK2 substantially enhances the surface expression of the human OSMR.”

What the sources say

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  cites [49]

In the paper

“Recently, it has been found that TYK2 prevents receptor internalization [69].”

What the sources say

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  cites [69]

In the paper

“Similarly, JAK2 is crucial for EpoR surface expression.”

What the sources say

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  cites [59]

In the paper

“This, together with the lack of reports by other groups confirming the phosphorylation of Tyr 657 , questions the relevance of this tyrosine phosphorylation site for STAT3 function.”

In the paper

“For several cell lines it has been reported that PKCδ associates IL-6 dependently with STAT3 and phosphorylates it on Ser 727 , leading to an inhibition of STAT3 DNA binding and transcriptional activity [94].”

What the sources say

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  cites [94]

In the paper

“Finally, also the interbox1-2 region of gp130 is critical, e.g.mutation of a single amino acid (Trp 666 ) abrogates JAK binding and thereby leads to inactivation of the receptor complex [54].”

What the sources say

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  cites [54]

In the paper

“Phosphorylation of this Tyr 657 would severely impair the function of the SH2 domain, as it is located in the centre of the binding pocket responsible for specific recognition of phosphotyrosine motifs.”

In the paper

“The Src family kinase Hck has recently been shown to associate with an acidic region (amino acids 771-811) of gp130 [65].”

What the sources say

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  cites [65]

In the paper

“However, the location of Tyr 657 in the solved structure of STAT3β bound to DNA questions that Tyr 657 is able to recruit the SH2 domain of PI3K.”

In the paper

“Whereas STAT3 binds to phospho (p)YXXQ motifs (Y 767 RHQ, Y 814 FKQ, Y 905 LPQ and Y 915 MPQ in gp130; Y 981 QPQ, Y 1001 KPQ and Y 1028 RPQ in LIFR) [81,[84][85][86]”

What the sources say

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  cites [81,[84][85][86]

In the paper

“Signal transduction is even drastically impaired if only one chain within a gp130 dimer carries the W652A mutation [55].”

What the sources say

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  cites [55]

In the paper

“PKCδ (protein kinase Cδ), a kinase implicated in serine phosphorylation of STAT3 (see below), has been found in a complex with gp130 upon IL-6 stimulation.”

What the sources say

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  cites [67]

In the paper

“Subsequent to receptor binding, the STAT factors are phosphorylated on a single tyrosine residue (Tyr 701 in STAT1 and Tyr 705 in STAT3) [88,89].”

What the sources say

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  cites [88]
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  cites [89]

In the paper

“association of the JAKs to the box1/box2 region leads to the masking of a negative regulatory signal, potentially a previously uncharacterized endoplasmic reticulum retention/retrieval signal, that prevents efficient surface expression.”

What the sources say

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  cites [49]

In the paper

“Although several gp130 motifs mediate STAT3 activation, they are not equivalent with respect to their potential to activate STAT factors and acute-phase protein gene promoters [87].”

What the sources say

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  cites [87]

In the paper

“Interestingly, the STAT1 and STAT3 phosphotyrosine motifs (STAT1, pY 701 IKT; STAT3, pY 705 LKT) do not agree with the STAT3 consensus sequences deduced from the gp130 and LIFR recruitment sites [81,[84][85][86].”

What the sources say

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  cites [81,[84][85][86]

In the paper

“In addition, the partially buried side chain of Tyr 657 would not be able to bind into the phosphotyrosine binding pocket of PI3K.”

In the paper

“A recent mutagenesis study has highlighted the importance of the F1 subdomain of JAK1 for the interaction with gp130 [63].”

What the sources say

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  cites [63]

In the paper

“it was described that alteration of the kinase domain structure of JAK3 by the kinase inhibitor staurosporine decreased the ability to bind to the common γ chain [64].”

What the sources say

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  cites [64]

In the paper

“TYK2 is important for surface expression of the IFNα receptor 1 chain [68].”

What the sources say

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  cites [68]

In the paper

“Most investigators have found an increase in transcription of target genes upon cytokine-induced serine phosphorylation of STAT1, -3 and -5 [93,[98][99][100][101][102].”

What the sources say

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  cites [93,[98][99][100][101][102]

In the paper

“Dephosphorylation of STAT within the nucleus leads to export from the nucleus [121].”

What the sources say

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  cites [121]

In the paper

“Artificially dimerized STAT proteins that are not phosphorylated also accumulate in the nucleus [110,111].”

What the sources say

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  cites [110]
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  cites [111]

In the paper

“Initial analyses concerning gp130-and LIFR-mediated activation of MAPKs identified the SHP2 (SH2-domain-containing tyrosine phosphatase)-binding site Tyr 759 of gp130 [81] and Tyr 974 of LIFR to be crucial for the activation of the MAPK cascade [127].”

What the sources say

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  cites [127]

In the paper

“The functional overlap of DNA-binding, NLS and NES sequences points to a role for DNA binding in the regulation of nucleocytoplasmic shuttling of STAT proteins.”

In the paper

“It has been demonstrated that the adaptor protein Shc (SH2and collagen-homology-domain-containing protein) (Figure 4) is recruited to the receptor via Tyr 861 in the cytoplasmic region of the OSMR [128] (Figure 6).”

What the sources say

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  cites [128]

In the paper

“Two other NESs were characterized in the coiled-coil region of STAT1 (residues 302-314), both containing several leucine residues that are critical for their function [109,120].”

What the sources say

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  cites [109]
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  cites [120]

In the paper

“Subsequently, tyrosine-phosphorylated SHP2 interacts with Grb2 [132].”

What the sources say

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  cites [132]

In the paper

“Nevertheless, mutation of Tyr 759 , the SHP2 recruitment site within gp130, impairs the interaction of Gab1 with SHP2 and PI3K, suggesting that binding of SHP2 to gp130 and its subsequent phosphorylation is a prerequisite for the interaction with Gab1.”

In the paper

“Further evidence suggests that continuous nucleocytoplasmic shuttling of STAT proteins even occurs after stimulation and nuclear accumulation [126].”

What the sources say

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  cites [126]

In the paper

“NLSs for this phosphorylation-independent shuttling are different from those for phosphorylation-induced nuclear accumulation, but are not yet identified [117].”

What the sources say

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  cites [117]

In the paper

“Thus there seems to exist no strict requirement for the targeted movement of endocytotic vesicles for STAT nuclear translocation to occur.”

In the paper

“Although Gab1 integrates several signal transduction pathways, translocation of SHP2 to the membrane, in proximity to membrane anchored Ras, seems to be sufficient to mediate ERK activation, since expression of a fusion protein comprising the PH domain of Gab1 and active SHP2 induces constitutive MEK1 (MAPK/ERK kinase) and ERK2 activation [137].”

What the sources say

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  cites [137]

In the paper

“Interestingly, no direct interaction of Gab1 and gp130 is required for its tyrosine phosphorylation.”

In the paper

“Adjacent to this sequence, basic residues (Lys 410 and Arg 413 ) were identified that also contribute to the NLS of dimeric STAT1 [117][118][119].”

What the sources say

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  cites [117]
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  cites [118]
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  cites [119]

In the paper

“Moreover, there is evidence that the PKCδ-mediated STAT3 Ser 727 phosphorylation occurs in the nucleus [95].”

What the sources say

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  cites [95]

In the paper

“Another degree of complexity is added by the fact that Gab1 is also involved in the activation of the Ras-Raf-MAPK cascade.”

In the paper

“Nevertheless, mutagenesis studies on STAT5 provided the first evidence for a functional role of the DNA-binding domain in nuclear translocation [115].”

What the sources say

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  cites [115]

In the paper

“In contrast with gp130 and LIFR, the OSMR does not recruit SHP2.”

In the paper

“Nevertheless, the OSMR is also able to induce activation of the Ras-Raf-MAPK pathway.”

In the paper

“The finding of unphosphorylated STAT proteins within the nucleus [122] is consistent with the well-established role of unphosphorylated STATs as transcriptional coactivators [124,125].”

What the sources say

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  cites [124]
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  cites [125]

In the paper

“Our recent investigations and work of others [117,122,123] led to the establishment of continous nucleocytoplasmic shuttling of STAT proteins that is independent from extracellular stimulation and phosphorylation.”

What the sources say

• ?Not matched

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  cites [117]
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  cites [122]
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  cites [123]

In the paper

“Initial analyses concerning gp130-and LIFR-mediated activation of MAPKs identified the SHP2 (SH2-domain-containing tyrosine phosphatase)-binding site Tyr 759 of gp130 [81] and Tyr 974 of LIFR to be crucial for the activation of the MAPK cascade [127].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [81]

In the paper

“Indeed, extracellularsignal-dependent translocation of STAT1 in response to IFN requires the nuclear import receptor NPI-1/importin-α5, which mediates translocation via a Ran-dependent mechanism [107].”

What the sources say

• ?Not matched

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  cites [107]

In the paper

“Thus the OSMR, unlike gp130 or the LIFR, uses the Shc-Grb2-SOS route for activation of MAPKs [128].”

What the sources say

• ?Not matched

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  cites [128]

In the paper

“Later it turned out that residues located within this short sequence stretch are important for the interaction of STAT1 with the import receptor importin-α5 and therefore for nuclear import of STAT1 [116,117].”

What the sources say

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  cites [116]
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  cites [117]

In the paper

“Nevertheless, mutation of Tyr 759 , the SHP2 recruitment site within gp130, impairs the interaction of Gab1 with SHP2 and PI3K, suggesting that binding of SHP2 to gp130 and its subsequent phosphorylation is a prerequisite for the interaction with Gab1.”

In the paper

“Finally, IL-6-induced association of Gab1 with SHP2 leads to activation of ERK2 [135].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [135]

In the paper

“The finding of unphosphorylated STAT proteins within the nucleus [122] is consistent with the well-established role of unphosphorylated STATs as transcriptional coactivators [124,125].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [122]

In the paper

“Similarly, PI3K associates with the IRS-1 (insulin receptor substrate-1) adaptor in response to OSM [150], suggesting that both IRS-1 and Gab1 may couple gp130 to PI3K activation.”

In the paper

“Binding of the SH2 domains to phosphotyrosine motifs of receptors or adapters unfolds the protein, leading to enzymic activity [153][154][155].”

What the sources say

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  cites [153]
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  cites [154]
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  cites [155]

In the paper

“Whereas PIAS1 specifically inhibits DNA binding of activated STAT1 and thus STAT1-mediated gene induction (after IFN stimulation) [179], PIAS3 was found to be specific for the inhibition of STAT3-mediated gene expression (after IL-6 stimulation) [178].”

What the sources say

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  cites [178]

In the paper

“Whereas PIAS1 specifically inhibits DNA binding of activated STAT1 and thus STAT1-mediated gene induction (after IFN stimulation) [179], PIAS3 was found to be specific for the inhibition of STAT3-mediated gene expression (after IL-6 stimulation) [178].”

What the sources say

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  cites [179]

In the paper

“Meanwhile, this phosphatase has been identified as the nuclear isoform of the T-cell PTP TC45 [174,175].”

What the sources say

• ?Not matched

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  cites [174]
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  cites [175]

In the paper

“Similarly, PI3K associates with the IRS-1 (insulin receptor substrate-1) adaptor in response to OSM [150], suggesting that both IRS-1 and Gab1 may couple gp130 to PI3K activation.”

What the sources say

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  cites [150]

In the paper

“The interaction of PIAS proteins with STAT factors seems to require tyrosine phosphorylation of the STAT proteins.”

In the paper

“Further evidence for STAT3 as a direct substrate of SHP2 comes from the detection of STAT3-SHP2 complexes [163].”

What the sources say

• ?Not matched

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  cites [163]

In the paper

“Since both T-cell PTP and PIAS1 associate with the N-terminus of STAT1 (see below), PIAS1 may prevent dephosphorylation by preferentially masking the T-cell PTP binding region of nonmethylated STAT1 [176].”

What the sources say

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  cites [176]

In the paper

“Moreover, in human Hep3B hepatoma cells IL-6 leads to activation of the PI3K/Akt pathway necessary for the anti-apoptotic effect of IL-6 during transforming growth factor β treatment [148].”

What the sources say

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  cites [148]

In the paper

“After IL-6 stimulation the adaptor protein Gab1 (see the subsection above entitled 'Activation of MAPK cascades: one tyrosine to make things more complicated') interacts with PI3K [135].”

What the sources say

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  cites [135]

In the paper

“In cardiac myocytes gp130 conveys signals through this pathway which lead to prevention of doxorubicin-induced apoptosis [143].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [143]

In the paper

“Tyr 759 of gp130 appears to have multivalent functions for signalling; substitution with phenylalanine impairs SHP2 recruitment and phosphorylation [81] and leads to enhanced 157,158], as well as LIF and OSM, signal transduction [159].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [81]

In the paper

“Overexpression of dominant-negative SHP2 mutants leads to enhanced receptor, JAK, STAT and SHP2 phosphorylation [160].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [160]

In the paper

“The crystal structure of SHP2 suggests that, in the absence of a tyrosinephosphorylated binding partner, the N-terminal SH2 domain covers the active site and thereby inhibits the enzymic activity [152].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [152]

In the paper

“IL-6-type cytokines can lead to the activation of yet an additional signalling cascade involving PI3K.”

In the paper

“In contrast with PIAS1, however, it did not affect STAT1 DNAbinding activity.”

In the paper

“First evidence for the contribution of a phosphatase in IL-6 signalling was obtained by the finding that the PTP SHP2 is recruited to the cytoplasmic Tyr 759 of activated gp130 [81,151].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [81]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [151]

In the paper

“In the case of STAT1, SHP2 has been described as a dual-specificity phosphatase that dephosphorylates pTyr 701 and pSer 727 [164].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [164]

In the paper

“Recently, PIASy was found to also inhibit STAT1-mediated gene activation [181].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [181]

In the paper

“As mentioned above, PIAS1 preferentially associates with unmethylated STAT1 [106].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [106]

In the paper

“However, SHP2 also plays a negative regulatory role as a tyrosine phosphatase in the Jak/STAT pathway [160] (as indicated in Figure 8).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [160]

In the paper

“Initially identified as Gu/RNA helicase II-binding protein (PIAS1) [177], it rapidly became clear that PIAS proteins are important transcriptional co-regulators of the JAK/STAT pathway [178,179].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [178]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [179]

In the paper

“Subsequently, these phosphotyrosines interact with the N-and C-terminal SH2-domains respectively, relieving the PTP domain from the N-terminal SH2-domain-mediated inhibition [156] (Figure 7).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [156]

In the paper

“Interestingly, STAT1 methylated at Arg 31 is a better substrate for T-cell PTP than non-methylated STAT1.”

In the paper

“SHP2 also becomes activated by the phosphorylation of tyrosine residues 542 or 580 within the C-terminal part of the enzyme.”

In the paper

“It was shown in MK2-deficient macrophages that the half-life of IL-6 mRNA was reduced by more than 10-fold.”

In the paper

“The KIR region is thought to bind to the substrate binding site of the kinase domain and thereby to inhibit its catalytic activity [195].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [195]

In the paper

“Consistent with the postulated E3-ligase function are new findings that SOCS1 targets JAK2, Tel-JAK2 and IRS1/2, as well as Vav, to degradation [208][209][210][211][212].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [208]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [209]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [210]

In the paper

“Both have been shown to act on the JAKs, and thereby inhibit the phosphorylation of gp130, STATs and the JAKs themselves [190,192].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [190]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [192]

In the paper

“In the case of SOCS3, tyrosine phosphorylation in response to IL-2, Epo, EGF and PDGF was reported [139,216].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [139]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [216]

In the paper

“PIASy rather appears to act as a transcriptional co-repressor of STAT1.”

In the paper

“In contrast with SOCS1, despite the fact that it can also bind to JAKs and that it contains a KIR region [196], SOCS3 associates with specific phosphotyrosine motifs within activated cytokine receptors, such as gp130, EpoR, leptin receptor and the granulocyte colony-stimulating factor receptor [197][198][199][200][201][202][203].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [197]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [198]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [199]

In the paper

“A similar mechanism has been discovered for IFNγ signalling, where LPS inhibits IFNγ -dependent STAT1 activation also via the induction of SOCS3 [230].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [230]

In the paper

“In fact, the affinity of SOCS3 to bind to gp130 peptides is even slightly higher than that of SHP2 [204].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [204]

In the paper

“The Janus kinases JAK1, JAK2, TYK2 and gp130 show intermediate half-lives.”

In the paper

“This inhibition is most likely due to induction of the de novo synthesis of the JAK-inhibitor SOCS3 [229].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [229]

In the paper

“Interestingly, the half-life of STAT3β, a splice variant of STAT3α, is reduced by almost 50 % compared with the half-life of STAT3α.”

In the paper

“Sumoylation may play a critical role in targeting transcription factors to nuclear bodies, where they bind to other sumoylated proteins, such as PML (promyelocytic leukaemia) or the co-repressor Sp100, and thereby become transcriptionally active or inactive [186,187].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [186]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [187]

In the paper

“The stress-activated p38 MAPK has been shown to play an important role in stabilizing the mRNA of many cytokines, including IL-6, by activation of MK2 (MAPKAPK2, MAPK-activated protein kinase 2) [217].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [217]

In the paper

“Binding studies with phosphopeptides suggest that SOCS3 binds pTyr 759 of gp130 with much higher affinity than pTyr 1007 within the activation loop of JAK2 [198].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [198]

In the paper

“For example, LPS (lipopolysaccharide) and the pro-inflammatory cytokine TNFα have been shown to inhibit IL-6-mediated STAT3 activation in macrophages.”

In the paper

“It has been reported that the half-lives of the various players involved in IL-6 signalling differ substantially (Table 1) [222,223].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [222]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [223]

In the paper

“Interestingly, both SOCS3-dependent and SOCS3-independent inhibitory mechanisms of pro-inflammatory stimuli depend on the p38 stress kinase [229,231,233].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [229]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [231]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [233]

In the paper

“Mutations within the box region of SOCS1, as well as serine phosphorylation, which disrupt elongin C binding, have been shown to stabilize SOCS1 [213,214].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [213]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [214]

In the paper

“While earlier studies suggested that PIAS proteins might act in the cytoplasm, the picture that emerges from recently published work is that at least some members of this family display their activity in the nucleus.Here, they are located in specific nuclear bodies [182,183] attached to the nuclear scaffold [184].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [182]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [183]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [184]

In the paper

“Recent work suggests that SOCS proteins may be part of E3-ubiquitin ligases in complex with elongins B and C, as well as Rbx1 (RING box protein 1) and Cul5 (cullin 5) [206,207].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [206]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [207]

In the paper

“With respect to this finding, it is of interest that PIAS proteins exhibit E3-SUMO (small ubiquitin-related modifier)-ligase activity [185,186].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [185]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [186]

In the paper

“Although both SOCS3 and SHP2 are recruited to the same site within the native gp130, it is suggested that there are two largely distinct modes of negative regulation of gp130 activity: through the feedback inhibition by SOCS3 and/or the dephosphorylation of phosphorylated JAKs, receptors and STATs [160].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [160]

In the paper

“CIS, which was the first member to be identified, was shown to compete with STAT5 for recruitment sites within the EpoR and to thereby modulate the JAK2/STAT5 pathway [189,194].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [189]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [194]

In the paper

“Additional mechanisms for inhibiting IL-6 signalling by pro-inflammatory cytokines may exist, since other data show that IL-1, TNF-α and LPS inhibit IL-6-dependent STAT activation in macrophages through mechanisms which do not depend on de novo protein synthesis [231,232].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [231]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [232]

In the paper

“SOCS1 inhibits signal transduction by binding to the activation loop of the JAKs via its SH2 domain.”

In the paper

“This difference in the inhibitory mechanisms of SOCS1 and SOCS3 is also reflected in the fact that SOCS1 blocks JAK activity more efficiently than SOCS3 [205].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [205]

In the paper

“Thus, EZI may augment STAT3 activity by keeping it in the nucleus.”

In the paper

“By a similar mechanism STAT5B limits NF-κB-mediated signalling [254].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [254]

In the paper

“This tandem organization of STAT-binding sites has also been emphasized to be essential for binding of tetrameric STAT3 to the α 2 M promoter [245].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [245]

In the paper

“Interestingly, although NF-κB acts as a competitive inhibitor for STAT3 DNA-binding, at least one intact NF-κB and one intact STAT3 consensus site is crucial for the STAT3-dependent activation of the α 2 M gene promoter [236], suggesting that a balanced ratio of NF-κB and STAT3 is essential for activating the α 2 M promoter.”

In the paper

“Instead ERK1/2 MAPK were found to play a crucial role [234].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [234]

In the paper

“STAT-binding sites are often in close proximity to binding sites for other transcription factors, such as nuclear factor-IL6 [237], NF-κB [238], activator protein-1 [224,[239][240][241] and glucocorticoid receptor [242], making a co-operative action of these factors with STATs in gene regulation most likely.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [237]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [238]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [224]

In the paper

“STAT3 and EZI physically interact as demonstrated by co-immunoprecipitation.”

In the paper

“The C-terminal transactivation domains of STAT1, STAT3 and STAT5 are known to interact with CBP/p300 [239,[250][251][252].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [239]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [250]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [251]

In the paper

“FKHR is inactivated by Akt/protein kinase B-mediated serine/threonine phosphorylation.”

In the paper

“Binding of the N-or C-terminal SH2 domain by specific phosphotyrosine-containing motifs releases the block.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [156]

In the paper

“Moreover, in the promoters of the rat α 2 M and the human α 1antichymotrypsin genes, STAT3-binding sites are arranged as a tandem [243,244], suggesting that formation of multimers on clustered binding sites also represents a regulatory step in STATdependent gene activation.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [243]
• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [244]

In the paper

“IL-1β is also known to inhibit IL-6-induced acute-phase protein synthesis in hepatocytes [235].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [235]

In the paper

“In the inactive state, the N-terminal SH2 domain of SHP2 sterically hinders access of phosphotyrosine substrates to the PTP domain and thus blocks PTPase activity.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [156]

In the paper

“Interestingly, although NF-κB acts as a competitive inhibitor for STAT3 DNA-binding, at least one intact NF-κB and one intact STAT3 consensus site is crucial for the STAT3-dependent activation of the α 2 M gene promoter [236], suggesting that a balanced ratio of NF-κB and STAT3 is essential for activating the α 2 M promoter.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [236]

In the paper

“The first evidence for a competition of STAT3 and NF-κB for the α 2 M promoter binding was provided by Zhang and Fuller [246] on an isolated binding site within the α 2 M promoter.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [246]

In the paper

“These results indicate that FKHR can modulate the IL-6-induced transcriptional activity by enhancing STAT3 action.”

In the paper

“This indicates a dual, negative as well as positive, regulatory function of NF-κB in acute-phase protein gene induction.”

In the paper

“Such a regulatory function has been shown for STAT1 which abolishes activator protein-1/ets transcriptional activity by competing for CBP binding [239].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [239]

In the paper

“Instead, NF-κB was identified as a mediator for IL-1β-dependent suppression of IL-6-induced α 2 M (α 2 -macroglobulin) expression in liver cells [236].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [236]