SOCS3
外观
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细胞因子信号传导抑制因子3(SOCS3或 SOCS-3)是一种在人体内由 SOCS3基因编码的蛋白。[5][6] 该基因编码 STAT- 诱导的 STAT 抑制子(SSI),也可称为细胞因子信号转导(SOCS)家族抑制子,的一个成员。 SSI 家族成员是可由细胞因子诱导的细胞因子信号转导负调节因子。
功能
[编辑]SOCS3基因的表达可由多种细胞因子的诱导,包括 IL-6,IL-10,干扰素-γ(IFN-γ)。
在 IL-6,Epo,GCSF 和瘦素的信号传导中,已发现SOCS3在各自的细胞因子受体上的结合对 SOCS3的抑制功能而言是至关重要的。
SOCS3的过表达会抑制脂肪组织和肝脏胰岛素信号转导,但对肌肉则不然。[7] 但是在小鼠骨骼肌中敲除 SOCS3可以保护小鼠免于肥胖相关的胰岛素抵抗。[7]
由于神经酰胺合成的增加,SOCS3会增加瘦素抵抗和胰岛素抵抗。[8] 因此,研究已表明去除 SOCS 基因可以预防肥胖症患者的胰岛素抵抗[7]
对该小鼠中基因的同源基因的研究表明,该基因在胎儿肝脏造血和胎盘发育的负调控中发挥作用。[9]
SOCS3蛋白能与JAK2结合,抑制其活性。
相互作用
[编辑]已经证明 SOCS3可以与下列物质相互作用:
调控
[编辑]有部分证据表明 SOCS3的表达受小分子核糖核酸 miR-203的调控。[16][17]
参见
[编辑]参考文献
[编辑]- ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000184557 - Ensembl, May 2017
- ^ 2.0 2.1 2.2 GRCm38: Ensembl release 89: ENSMUSG00000053113 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3. Biochem Biophys Res Commun. September 1997, 237 (1): 79–83. PMID 9266833. doi:10.1006/bbrc.1997.7080.
- ^ 6.0 6.1 Cloning and characterization of novel CIS family genes. Biochem Biophys Res Commun. November 1997, 239 (2): 439–46. PMID 9344848. doi:10.1006/bbrc.1997.7484.
- ^ 7.0 7.1 7.2 Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity. Diabetes. 2013, 62 (1): 56–64 [2018-11-22]. PMC 3526029
. PMID 22961088. doi:10.2337/db12-0443. (原始内容存档于2018-11-23). 引用错误:带有name属性“pmid22961088”的
<ref>
标签用不同内容定义了多次 - ^ Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome. American Journal of Physiology. 2009, 297 (1): E211–E224 [2018-11-22]. PMC 2711669
. PMID 19435851. doi:10.1152/ajpendo.91014.2008. (原始内容存档于2016-08-10).
- ^ Entrez Gene: SOCS3 suppressor of cytokine signaling 3. (原始内容存档于2010-03-07).
- ^ 10.0 10.1 CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2. J. Biol. Chem. September 2000, 275 (38): 29338–47. PMID 10882725. doi:10.1074/jbc.M003456200.
- ^ A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor. Eur. J. Biochem. May 2002, 269 (10): 2516–26. PMID 12027890. doi:10.1046/j.1432-1033.2002.02916.x.
- ^ 12.0 12.1 SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130. J. Biol. Chem. January 2003, 278 (1): 661–71. PMID 12403768. doi:10.1074/jbc.M210552200.
- ^ Suppressor of cytokine signaling (SOCS)-3 protein interacts with the insulin-like growth factor-I receptor. Biochem. Biophys. Res. Commun. November 2000, 278 (1): 38–43. PMID 11071852. doi:10.1006/bbrc.2000.3762.
- ^ 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. June 1999, 4 (6): 339–51. PMID 10421843. doi:10.1046/j.1365-2443.1999.00263.x.
- ^ Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras. Nat. Cell Biol. May 2001, 3 (5): 460–5. PMID 11331873. doi:10.1038/35074525.
- ^ miR-203 represses 'stemness' by repressing DeltaNp63.. Cell Death Differ. 2008, 15 (7): 1187–95. PMID 18483491. doi:10.1038/cdd.2008.69.
- ^ The expression of microRNA-203 during human skin morphogenesis.. Exp Dermatol. 2010, 19 (9): 854–6. PMID 20698882. doi:10.1111/j.1600-0625.2010.01118.x.
扩展阅读
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- Kile BT, Schulman BA, Alexander WS, Nicola NA, Martin HM, Hilton DJ (2002). "The SOCS box: a tale of destruction and degradation". Trends Biochem. Sci. 27 (5): 235–41. doi:10.1016/S0968-0004(02)02085-6. PMID 1276535(页面存档备份,存于互联网档案馆).
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- Sasaki A, Yasukawa H, Suzuki A, Kamizono S, Syoda T, Kinjyo I, Sasaki M, Johnston JA, Yoshimura A (1999). "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. doi:10.1046/j.1365-2443.1999.00263.x. PMID 10421843(页面存档备份,存于互联网档案馆).
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- Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A (2000). "CIS3/SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2". J. Biol. Chem. 275 (38): 29338–47. doi:10.1074/jbc.M003456200. PMID 10882725(页面存档备份,存于互联网档案馆).
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- Bjorbak C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, Myers MG (2001). "SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985". J. Biol. Chem. 275 (51): 40649–57. doi:10.1074/jbc.M007577200. PMID 11018044(页面存档备份,存于互联网档案馆).
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