Find SOCS1 Products Interaction Network for SOCS1 SOCS1 Details

Related Pathways JAK/Stat Signaling IL-2 Signaling IL-6 Signaling View All Pathways

Synonyms: CIS1, CISH1, Cish7, JAB, JBP, SOCS1, Sosc1, SSI-1, STAT INDUCED STAT INHIBITOR-1, TIP3

SOCS Pathway

The suppressor of cytokine signaling (SOCS) family is composed of SOCS-1/SSI-1/JAB-1/TIP3; SOCS-2; SOCS-3 to SOCS-7 and cytokine-inducible SH2-containing protein (CIS). SOCS proteins are cytokine-induced negative feedback-loop regulators of cytokine signal transduction, especially pathways involving JAK/STAT signaling. SOCS proteins are involved in the down regulation of a variety of cytokines including interferon gamma (IFNgamma), growth hormone (GH), erythropoietin (EPO), granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor (G-CSF), IL-2, IL-3, IL-6, leptin, IL-12. SOCS-1 and SOC-3 have been linked to cytokine induced insulin resistance via ubiquitin proteosome mediated degradation of IRS-1 and IRS-2. SOCS have been linked to the degradation of the guanine nucleotide exchange factor (GEF) Vav, and focal adhesion kinase (FAK). The specificity of SOCS action is dependent upon the SOCS isoform.

SOCS proteins, CIS, SOCS-1, SOCS-2 and SOCS3, inhibit cytokine-activated Janus kinase/signal transducers and activators of transcription (JAK/ STAT) signaling pathways. SOCS proteins contain a central src homology 2 domain (SH2), a C-terminal SOCS box and unique N-termini. SOCS proteins employ three primary mechanisms to inhibit cytokine signaling. SOCS SH2 domains interact with phosphorylated JAK proteins and other non-receptor protein kinases and inactivate them or with cytokine receptors wherein they block STAT protein binding and activation. The SOCS box in the C-terminal targets molecules associated with SOCS proteins to proteosome mediated degradation via a mechanism that involves binding of elongins B and C and the E3 ubiquitin ligase complex.