Cytokine signaling mediated by the JAK-STAT pathway plays essential roles in differentiation, maturation, proliferation and apoptosis of a various types of cells. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the JAK-STAT signaling pathway. SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers []. All SOCS share a central SH2 domain and a C-terminal SOCS box, but only SOCS1 and SOCS3 possess a kinase inhibitory region immediately upstream of the central SH2 [].SOCS1 plays a key role in the negative regulation of interferon-gamma signaling and in T cell differentiation [, , ].
CUE domain containing 2 (CUEDC2) is involved in the regulation of the cell cycle, inflammation, and tumorigenesis []. It interacts with progesterone receptor (PR) and promotes progesterone-induced PR degradation by the ubiquitin-proteasome pathway []. It also interacts with SOCS1 to to suppress SOCS1's ubiquitin-mediated degradation [].
Cytokine signaling mediated by the JAK-STAT pathway plays essential roles in differentiation, maturation, proliferation and apoptosis of a various types of cells. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the JAK-STAT signaling pathway. SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers []. All SOCS share a central SH2 domain and a C-terminal SOCS box, but only SOCS1 and SOCS3 possess a kinase inhibitory region immediately upstream of the central SH2 [].SOCS3 interacts with gp130, a common cytokine receptor for interleukin (IL)-6, leukemia inhibitory factor (LIF) and other members of the IL-6 family of cytokines. SOCS3 has been reported also to interact with the leptin receptor, erythropoietin receptor, insulin receptor, IL-12beta receptor and granulocyte-colony stimulating factor receptor [].
Cytokine signaling mediated by the JAK-STAT pathway plays essential roles in differentiation, maturation, proliferation and apoptosis of a various types of cells. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the JAK-STAT signaling pathway. SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers []. All SOCS share a central SH2 domain and a C-terminal SOCS box, but only SOCS1 and SOCS3 possess a kinase inhibitory region immediately upstream of the central SH2 [].SOCS2 is necessary for normal growth regulation []. It appears to be a negative regulator in the growth hormone/IGF1 signaling pathway [, ].
This entry represents the SH2 domain of SOCS3.Cytokine signaling mediated by the JAK-STAT pathway plays essential roles in differentiation, maturation, proliferation and apoptosis of a various types of cells. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the JAK-STAT signaling pathway. SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers []. All SOCS share a central SH2 domain and a C-terminal SOCS box, but only SOCS1 and SOCS3 possess a kinase inhibitory region immediately upstream of the central SH2 [].SOCS3 interacts with gp130, a common cytokine receptor for interleukin (IL)-6, leukemia inhibitory factor (LIF) and other members of the IL-6 family of cytokines. SOCS3 has been reported also to interact with the leptin receptor, erythropoietin receptor, insulin receptor, IL-12beta receptor and granulocyte-colony stimulating factor receptor [].
This entry represents the SH2 domain of SOCS1.Cytokine signaling mediated by the JAK-STAT pathway plays essential roles in differentiation, maturation, proliferation and apoptosis of a various types of cells. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the JAK-STAT signaling pathway. SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers []. All SOCS share a central SH2 domain and a C-terminal SOCS box, but only SOCS1 and SOCS3 possess a kinase inhibitory region immediately upstream of the central SH2 [].SOCS1 plays a key role in the negative regulation of interferon-gamma signaling and in T cell differentiation [, , ].
This entry represents the SH2 domain of SOCS2.Cytokine signaling mediated by the JAK-STAT pathway plays essential roles in differentiation, maturation, proliferation and apoptosis of a various types of cells. Suppressor of cytokine signaling (SOCS) proteins are negative feedback regulators of the JAK-STAT signaling pathway. SOCS1 and SOCS3 are potent inhibitors of JAKs and can play pivotal roles in inflammation, as well as in the development and progression of cancers []. All SOCS share a central SH2 domain and a C-terminal SOCS box, but only SOCS1 and SOCS3 possess a kinase inhibitory region immediately upstream of the central SH2 [].SOCS2 is necessary for normal growth regulation []. It appears to be a negative regulator in the growth hormone/IGF1 signaling pathway [, ].
STAT6 mediate signals from the IL-4 receptor. Unlike the other STAT proteins which bind an IFNgamma Activating Sequence (GAS), STAT6 stands out as having a unique binding site preference. This site consists of a palindromic sequence separated by a 3 bp spacer (TTCNNNG-AA)(N3 site). STAT6 is able to bind the GAS site but only at a low affinity upon IL-4-induced activation []. There is speculation that the inappropriate activation of STAT6 is involved in uncontrolled cell growth in an oncogenic state []. IL-4 signaling via STAT6 initially occurs unopposed, but is then dampened by a negative feedback mechanism through the IL-4/Stat6 dependent induction of SOCS1 expression. The IL-4 dependent aspect of Th2 differentiation requires the activation of STAT6. IL-4 signaling and STAT6 appear to play an important role in the immune response. It was shown that large scale chromatin remodeling of the IL-4 gene occurs as cells differentiate into Th2 effectors is STAT6 dependent []. This entry represents the SH2 domain of STAT6.STAT proteins have a dual function: signal transduction and activation of transcription. When cytokines are bound to cell surface receptors, the associated Janus kinases (JAKs) are activated, leading to tyrosine phosphorylation of the given STAT proteins []. Phosphorylated STATs form dimers, translocate to the nucleus, and bind specific response elements to activate transcription of target genes []. STAT proteins contain an N-terminal domain (NTD), a coiled-coil domain (CCD), a DNA-binding domain (DBD), an α-helical linker domain (LD), an SH2 domain, and a transactivation domain (TAD). The SH2 domain is necessary for receptor association and tyrosine phosphodimer formation. There are seven mammalian STAT family members which have been identified: STAT1, STAT2, STAT3, STAT4, STAT5 (STAT5A and STAT5B), and STAT6 [].
