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c -1.7431 -4.4582 4.0258 -4.312 -2.8225 -1.512 l -2.3501 -5.8375 l -3.8567 -15.8689 l -3.7191 -12.547 l -6.6611 4.825 c -4.4582 1.7431 -4.312 -4.0258 -1.512 2.8225 l -5.8375 2.3501 l -15.8689 3.8567 l -12.547 3.7191 l 4.825 6.6611 c 1.7431 4.4582 -4.0258 4.312 2.8225 1.512 l 2.3501 5.8375 l 3.8567 15.8689 l 3.7191 12.547 l 6.6611 -4.825 c 4.4582 -1.7431 4.312 4.0258 1.512 -2.8225 l 5.8375 -2.3501 l 15.8689 -3.8567 l 12.547 -3.7191 z" /> </svg> <svg contentScriptType="text/ecmascript" width="60.0" xmlns:xlink="http://www.w3.org/1999/xlink" zoomAndPan="magnify" style="overflow:visible;enable-background:new 0 0 60.0 60.0" contentStyleType="text/css" height="60.0" viewBox="0 0 60.0 60.0" preserveAspectRatio="xMidYMid meet" xmlns="http://www.w3.org/2000/svg" version="1.0"> <defs> <radialGradient id="MO_678658" gradientUnits="objectBoundingBox" spreadMethod="pad" xlink:show="other" xlink:type="simple" r="50%" cx="50%" fx="50%" fy="50%" cy="50%" xlink:actuate="onLoad"> <stop offset="0%" style="stop-color:white;stop-opacity:1;"/> <stop offset="100%" style="stop-color:#678658;stop-opacity:1;"/> </radialGradient> </defs> <path style="fill:url(#MO_678658);stroke:none;" d="M 60 42.4266 l -4.825 -6.6611 c -1.7431 -4.4582 4.0258 -4.312 -2.8225 -1.512 l -2.3501 -5.8375 l -3.8567 -15.8689 l -3.7191 -12.547 l -6.6611 4.825 c -4.4582 1.7431 -4.312 -4.0258 -1.512 2.8225 l -5.8375 2.3501 l -15.8689 3.8567 l -12.547 3.7191 l 4.825 6.6611 c 1.7431 4.4582 -4.0258 4.312 2.8225 1.512 l 2.3501 5.8375 l 3.8567 15.8689 l 3.7191 12.547 l 6.6611 -4.825 c 4.4582 -1.7431 4.312 4.0258 1.512 -2.8225 l 5.8375 -2.3501 l 15.8689 -3.8567 l 12.547 -3.7191 z" /> </svg> PMID: 14644140,9129017,10585430 The SH2 domain of the CIS associates with STAT5-binding sites of various types of receptor, including growth hormone (GH) receptors and EPO receptors PMID: 14644140,9129017,10585430 The SH2 domain of the CIS associates with STAT5-binding sites of various types of receptor, including growth hormone (GH) receptors and EPO receptors PMID: 14644140,7796808 Initial in vitro studies reported CIS as an inhibitor of the signal transduction of EPO, interleukin-2 (IL-2), IL-3, GH and prolactin, by masking the STAT5-binding sites of receptors and inhibiting the activation of STAT5. PMID: 14644140,7796808 Initial in vitro studies reported CIS as an inhibitor of the signal transduction of EPO, interleukin-2 (IL-2), IL-3, GH and prolactin, by masking the STAT5-binding sites of receptors and inhibiting the activation of STAT5. PMID: 14644140,7796808 Initial in vitro studies reported CIS as an inhibitor of the signal transduction of EPO, interleukin-2 (IL-2), IL-3, GH and prolactin, by masking the STAT5-binding sites of receptors and inhibiting the activation of STAT5. PMID: 14644140,7796808 Initial in vitro studies reported CIS as an inhibitor of the signal transduction of EPO, interleukin-2 (IL-2), IL-3, GH and prolactin, by masking the STAT5-binding sites of receptors and inhibiting the activation of STAT5. indirect PMID: 14644140,10453004,11390452,12433365,12433373,11208867 However, SOCS-1 expression is now known to be induced by insulin, lipopolysaccharide (LPS), CpG DNA and other molecules that do not use STATs in signal transduction indirect PMID: 14644140,10453004,11390452,12433365,12433373,11208867 However, SOCS-1 expression is now known to be induced by insulin, lipopolysaccharide (LPS), CpG DNA and other molecules that do not use STATs in signal transduction indirect PMID: 14644140,10453004,11390452,12433365,12433373,11208867 However, SOCS-1 expression is now known to be induced by insulin, lipopolysaccharide (LPS), CpG DNA and other molecules that do not use STATs in signal transduction PMID: 14644140 Based on the results of in vitro studies using cell lines forcedly expressing SOCS-1, it has been confirmed that SOCS-1 inhibits various types of signal transduction through its binding to JAK and possibly other signaling molecules, such as Vav, IRS-1 sand IL-1 receptor-associated kinase (IRAK) PMID: 14644140 Currently, SOCS-1 is thought to inhibit the catalytic activity of JAKs by directly binding to the JAK activation loop with both its SH2 and KIR domains and preventing the access of JAK substrates with its KIR domain. PMID: 14644140 Based on the results of in vitro studies using cell lines forcedly expressing SOCS-1, it has been confirmed that SOCS-1 inhibits various types of signal transduction through its binding to JAK and possibly other signaling molecules, such as Vav, IRS-1 sand IL-1 receptor-associated kinase (IRAK) PMID: 14644140 Based on the results of in vitro studies using cell lines forcedly expressing SOCS-1, it has been confirmed that SOCS-1 inhibits various types of signal transduction through its binding to JAK and possibly other signaling molecules, such as Vav, IRS-1 sand IL-1 receptor-associated kinase (IRAK) PMID: 14644140 Based on the results of in vitro studies using cell lines forcedly expressing SOCS-1, it has been confirmed that SOCS-1 inhibits various types of signal transduction through its binding to JAK and possibly other signaling molecules, such as Vav, IRS-1 sand IL-1 receptor-associated kinase (IRAK) PMID: 14644140,12208853,10403376 SOCS-2 is known to bind to the SHP2-binding site of activated GH receptors and to inhibit the activation of STAT5b induced by GH indirect PMID: 14644140,12208853,10403376 SOCS-2 is known to bind to the SHP2-binding site of activated GH receptors and to inhibit the activation of STAT5b induced by GH indirect indirect Growth promotion by GH is dependent on the induction of insulin-like growth factor-1 (IGF-1) by GH, whereas SOCS-2-deficient mice do not exhibit an increase in serum IGF-1. PMID: 14644140,12208853,9727029 SOCS-2 binds not only to GH receptors but also to IGF-1 receptors indirect PMID: 14644140,11331873 In addition, in vitro data have suggested that SOCS-3 undergoes tyrosine-phosphorylation on stimulation with IL-2 and appears to accelerate the activation of ErK (extracellular-signal-regulated kinase) by acting as an adaptor molecule indirect PMID: 14644140,11331873 In addition, in vitro data have suggested that SOCS-3 undergoes tyrosine-phosphorylation on stimulation with IL-2 and appears to accelerate the activation of ErK (extracellular-signal-regulated kinase) by acting as an adaptor molecule indirect indirect PMID: 14644140,9889194 SOCS-5 is induced in M1 cell lines in response to stimulation with IL-6 and marginally inhibits IL-6 signaling PMID: 14644140,11342531 SOCS-6 binds to insulin receptors and inhibits the activation of Erk1/2, protein kinase B and IRS-1 PMID: 14644140,11342531 SOCS-6 binds to insulin receptors and inhibits the activation of Erk1/2, protein kinase B and IRS-1 PMID: 14644140,11342531 SOCS-6 binds to insulin receptors and inhibits the activation of Erk1/2, protein kinase B and IRS-1 PMID: 14644140,11342531 SOCS-6 binds to insulin receptors and inhibits the activation of Erk1/2, protein kinase B and IRS-1 PMID: 14644140,11342531 SOCS-6 binds to insulin receptors and inhibits the activation of Erk1/2, protein kinase B and IRS-1 PMID: 14644140,12052866 Interestingly, a recent study has reported that SOCS-6 binds to IRS-4, a molecule with an important role in insulin signaling, and that SOCS-6-deficient mice exhibit mild growth retardation PMID: 14644140,12626585 It is noteworthy that this notion is in line with the recent finding that SOCS-3 associates with gp130 but not with the IL-10 receptor (IL-10R), and endogenous SOCS-3 induced by cytokines inhibits IL-6 signaling but not IL-10 signaling in human macrophages PMID: 14644140 SOCS-3 inhibits the function of JAK by binding to the Src homology phosphatase-2 (SHP-2)-binding domain of gp130 and the EPORs PMID: 14644140 SOCS-3 inhibits the function of JAK by binding to the Src homology phosphatase-2 (SHP-2)-binding domain of gp130 and the EPORs indirect PMID: 14644140,12754506 Other groups showed that IL-6 strongly activates STAT1 and induces the expression of IFN-responsive genes in SOCS-3 deficient macrophages, implying that IL-6 could mimic the action of IFNs indirect PMID: 14644140,12754506 Other groups showed that IL-6 strongly activates STAT1 and induces the expression of IFN-responsive genes in SOCS-3 deficient macrophages, implying that IL-6 could mimic the action of IFNs PMID: 14644140,9774439 CIS is also involved in the ubiquitination and degradation of EPO receptors PMID: 14644140,9774439 CIS is also involved in the ubiquitination and degradation of EPO receptors PMID: 14644140,10747851,12228220,11971965 Indeed, SOCS-1 accelerates ubiquitination and degradation of Vav, insulin receptor substrate-1 (IRS-1) and JAKs that can associate with SOCS-1 PMID: 14644140,10747851,12228220,11971965 Indeed, SOCS-1 accelerates ubiquitination and degradation of Vav, insulin receptor substrate-1 (IRS-1) and JAKs that can associate with SOCS-1 PMID: 14644140,10747851,12228220,11971965 Indeed, SOCS-1 accelerates ubiquitination and degradation of Vav, insulin receptor substrate-1 (IRS-1) and JAKs that can associate with SOCS-1 PMID: 14644140,10747851,12228220,11971965 Indeed, SOCS-1 accelerates ubiquitination and degradation of Vav, insulin receptor substrate-1 (IRS-1) and JAKs that can associate with SOCS-1 PMID: 14644140,10747851,12228220,11971965 Indeed, SOCS-1 accelerates ubiquitination and degradation of Vav, insulin receptor substrate-1 (IRS-1) and JAKs that can associate with SOCS-1 PMID: 14644140,10747851,12228220,11971965 Indeed, SOCS-1 accelerates ubiquitination and degradation of Vav, insulin receptor substrate-1 (IRS-1) and JAKs that can associate with SOCS-1 PMID: 14644140,7796808 Initial in vitro studies reported CIS as an inhibitor of the signal transduction of EPO, interleukin-2 (IL-2), IL-3, GH and prolactin, by masking the STAT5-binding sites of receptors and inhibiting the activation of STAT5. PMID: 14644140,7796808 Initial in vitro studies reported CIS as an inhibitor of the signal transduction of EPO, interleukin-2 (IL-2), IL-3, GH and prolactin, by masking the STAT5-binding sites of receptors and inhibiting the activation of STAT5. PMID: 14644140,7796808 Initial in vitro studies reported CIS as an inhibitor of the signal transduction of EPO, interleukin-2 (IL-2), IL-3, GH and prolactin, by masking the STAT5-binding sites of receptors and inhibiting the activation of STAT5. PMID: 14644140,7796808 Initial in vitro studies reported CIS as an inhibitor of the signal transduction of EPO, interleukin-2 (IL-2), IL-3, GH and prolactin, by masking the STAT5-binding sites of receptors and inhibiting the activation of STAT5. PMID: 14644140,7796808 Initial in vitro studies reported CIS as an inhibitor of the signal transduction of EPO, interleukin-2 (IL-2), IL-3, GH and prolactin, by masking the STAT5-binding sites of receptors and inhibiting the activation of STAT5. PMID: 14644140,12208853,10403376 SOCS-2 is known to bind to the SHP2-binding site of activated GH receptors and to inhibit the activation of STAT5b induced by GH