SOCS3
Description
The SOCS3 (suppressor of cytokine signaling 3) is a protein-coding gene located on chromosome 17.
SOCS3 is a protein encoded by the SOCS3 gene. It is a member of the STAT-induced STAT inhibitor (SSI) family, also known as the suppressor of cytokine signaling (SOCS) family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. SOCS3 is a conserved gene found across the animal kingdom, including Drosophila, chickens, and crocodiles. The expression of the SOCS3 gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. Binding of SOCS3 to the respective cytokine receptor is crucial for its inhibitory function in the signaling of IL-6, Epo, GCSF, and Leptin. Overexpression of SOCS3 inhibits insulin signaling in adipose tissue and the liver, but not in muscle. However, deletion of SOCS3 in the skeletal muscle of mice protects against obesity-related insulin resistance. SOCS3 contributes to both leptin resistance and insulin resistance due to increased ceramide synthesis. Studies have shown that removing the SOCS gene prevents insulin resistance in obesity. Studies in mice suggest that SOCS3 plays roles in the negative regulation of fetal liver hematopoiesis and placental development.
SOCS3 is a key component of the negative feedback system regulating cytokine signaling. It acts as an inhibitor of cytokines that signal through the JAK/STAT pathway. SOCS3 binds to tyrosine kinase receptors such as IL6ST/gp130, LIF, erythropoietin, insulin, IL12, GCSF, and leptin receptors, blocking signal transduction. By binding to JAK2, SOCS3 suppresses its kinase activity, thereby regulating IL6 signaling. SOCS3 also plays a role in suppressing erythropoiesis in the fetal liver and regulates the development of allergic responses mediated by T-helper type 2 cells. SOCS3 acts as a substrate recognition component in an E3 ubiquitin-protein ligase complex, promoting ubiquitination and degradation of target proteins.
SOCS3 is also known as ATOD4, CIS3, Cish3, SOCS-3, SSI-3, SSI3.
