Biology:SOCS3
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Suppressor of cytokine signaling 3 (SOCS3 or SOCS-3) is a protein that in humans is encoded by the SOCS3 gene.[1][2] This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling.
SOCS3 is a conserved gene, found in across the animal kingdom, including Drosophila,[3] chickens,[4] and crocodiles.[5]
Function
The expression of SOCS3 gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma.
For signaling of IL-6, Epo, GCSF and Leptin, binding of SOCS3 to the respective cytokine receptor has been found to be crucial for the inhibitory function of SOCS3.
Overexpression of SOCS3 inhibits insulin signaling in adipose tissue and the liver, but not in muscle.[6] But deletion of SOCS3 in the skeletal muscle of mice protects against obesity-related insulin resistance.[6]
SOCS3 contributes to both leptin resistance and insulin resistance as a result of increased ceramide synthesis.[7] For that reason, studies have shown that removal of the SOCS gene prevents against insulin resistance in obesity[6]
Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development.[8]
The SOCS3 protein can bind to JAK2 kinase, and inhibits the activity of JAK2 kinase.
Interactions
SOCS3 has been shown to interact with:
- Erythropoietin receptor,[9][10]
- Glycoprotein 130,[11]
- Insulin-like growth factor 1 receptor,[12]
- Janus kinase 2,[2][9][13]
- PTPN11,[11] and
- RAS p21 protein activator 1.[14]
Regulation
There is some evidence that the expression of SOCS3 is regulated by the microRNA miR-203,[15][16] miR-409-3p and miR-1896.[17]
See also
References
- ↑ "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Biochem Biophys Res Commun 237 (1): 79–83. September 1997. doi:10.1006/bbrc.1997.7080. PMID 9266833.
- ↑ 2.0 2.1 "Cloning and characterization of novel CIS family genes". Biochem Biophys Res Commun 239 (2): 439–46. November 1997. doi:10.1006/bbrc.1997.7484. PMID 9344848.
- ↑ Stec, Wojciech; Vidal, Oscar; Zeidler, Martin P.; Chernoff, Jonathan (2013). "Drosophila SOCS36E negatively regulates JAK/STAT pathway signaling via two separable mechanisms". Molecular Biology of the Cell 24 (18): 3000–3009. doi:10.1091/mbc.e13-05-0275. ISSN 1059-1524. PMID 23885117.
- ↑ Nakanoh, Shota; Agata, Kiyokazu (2019). "Evolutionary view of pluripotency seen from early development of non-mammalian amniotes". Developmental Biology 452 (2): 95–103. doi:10.1016/j.ydbio.2019.04.014. ISSN 0012-1606. PMID 31029690.
- ↑ Xia, Tian; Zhang, Lei; Sun, Guolei; Yang, Xiufeng; Zhang, Honghai (2021). "Genomic evidence of adaptive evolution in the reptilian SOCS gene family". PeerJ 9: e11677. doi:10.7717/peerj.11677. ISSN 2167-8359. PMID 34221740.
- ↑ 6.0 6.1 6.2 "Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity". Diabetes 62 (1): 56–64. 2013. doi:10.2337/db12-0443. PMID 22961088. PMC 3526029. http://diabetes.diabetesjournals.org/content/62/1/56.long.
- ↑ "Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome". American Journal of Physiology 297 (1): E211–E224. 2009. doi:10.1152/ajpendo.91014.2008. PMID 19435851.
- ↑ "Entrez Gene: SOCS3 suppressor of cytokine signaling 3". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9021.
- ↑ 9.0 9.1 "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2". J. Biol. Chem. 275 (38): 29338–47. September 2000. doi:10.1074/jbc.M003456200. PMID 10882725.
- ↑ "A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor". Eur. J. Biochem. 269 (10): 2516–26. May 2002. doi:10.1046/j.1432-1033.2002.02916.x. PMID 12027890.
- ↑ 11.0 11.1 "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. 278 (1): 661–71. January 2003. doi:10.1074/jbc.M210552200. PMID 12403768.
- ↑ "Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor". Biochem. Biophys. Res. Commun. 278 (1): 38–43. November 2000. doi:10.1006/bbrc.2000.3762. PMID 11071852. https://zenodo.org/record/1229526.
- ↑ "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain". Genes Cells 4 (6): 339–51. June 1999. doi:10.1046/j.1365-2443.1999.00263.x. PMID 10421843.
- ↑ "Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras". Nat. Cell Biol. 3 (5): 460–5. May 2001. doi:10.1038/35074525. PMID 11331873.
- ↑ "miR-203 represses 'stemness' by repressing DeltaNp63.". Cell Death Differ 15 (7): 1187–95. 2008. doi:10.1038/cdd.2008.69. PMID 18483491.
- ↑ "The expression of microRNA-203 during human skin morphogenesis.". Exp Dermatol 19 (9): 854–6. 2010. doi:10.1111/j.1600-0625.2010.01118.x. PMID 20698882.
- ↑ Liu, Xiaomei; Zhou, Feng; Yang, Ying; Wang, Weixiao; Niu, Liping; Zuo, Dongjiao; Li, Xiangyang; Hua, Hui et al. (January 2019). "MiR-409-3p and MiR-1896 co-operatively participate in IL-17-induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3/STAT3 signaling". Glia 67 (1): 101–112. doi:10.1002/glia.23530. ISSN 1098-1136. PMID 30294880.
Further reading
- "Negative regulation of cytokine signaling pathways.". Annu. Rev. Immunol. 18: 143–64. 2000. doi:10.1146/annurev.immunol.18.1.143. PMID 10837055.
- "The SOCS box: a tale of destruction and degradation.". Trends Biochem. Sci. 27 (5): 235–41. 2002. doi:10.1016/S0968-0004(02)02085-6. PMID 12076535.
- "The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation.". Proc. Natl. Acad. Sci. U.S.A. 96 (5): 2071–6. 1999. doi:10.1073/pnas.96.5.2071. PMID 10051596. Bibcode: 1999PNAS...96.2071Z.
- "Cytokine-inducible SH2 protein-3 (CIS3/SOCS3) inhibits Janus tyrosine kinase by binding through the N-terminal kinase inhibitory region as well as SH2 domain.". Genes Cells 4 (6): 339–51. 1999. doi:10.1046/j.1365-2443.1999.00263.x. PMID 10421843.
- "SOCS3 is essential in the regulation of fetal liver erythropoiesis.". Cell 98 (5): 617–27. 1999. doi:10.1016/S0092-8674(00)80049-5. PMID 10490101.
- "SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130.". J. Biol. Chem. 275 (17): 12848–56. 2000. doi:10.1074/jbc.275.17.12848. PMID 10777583.
- "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms.". J. Biol. Chem. 274 (50): 35553–61. 2000. doi:10.1074/jbc.274.50.35553. PMID 10585430.
- "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2.". J. Biol. Chem. 275 (38): 29338–47. 2000. doi:10.1074/jbc.M003456200. PMID 10882725.
- "Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation.". J. Immunol. 165 (5): 2535–43. 2000. doi:10.4049/jimmunol.165.5.2535. PMID 10946280.
- "SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985.". J. Biol. Chem. 275 (51): 40649–57. 2001. doi:10.1074/jbc.M007577200. PMID 11018044.
- "IL-10 attenuates IFN-alpha-activated STAT1 in the liver: involvement of SOCS2 and SOCS3.". FEBS Lett. 480 (2–3): 132–6. 2000. doi:10.1016/S0014-5793(00)01905-0. PMID 11034314.
- "Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor". Biochem. Biophys. Res. Commun. 278 (1): 38–43. 2001. doi:10.1006/bbrc.2000.3762. PMID 11071852. https://zenodo.org/record/1229526.
- "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. 2001. doi:10.1101/gr.143000. PMID 11076863.
- "Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci". Nat. Genet. 27 (4): 372–3. 2001. doi:10.1038/86867. PMID 11279517.
- "Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras". Nat. Cell Biol. 3 (5): 460–5. 2001. doi:10.1038/35074525. PMID 11331873.
- "Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3". Proc. Natl. Acad. Sci. U.S.A. 98 (16): 9324–9. 2001. doi:10.1073/pnas.161271798. PMID 11481489. Bibcode: 2001PNAS...98.9324R.
- "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology 142 (12): 5286–93. 2001. doi:10.1210/endo.142.12.8549. PMID 11713228.
- "The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription". Biol. Chem. 382 (10): 1447–53. 2002. doi:10.1515/BC.2001.178. PMID 11727828.
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