SOCS3
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細胞因子信號傳導抑制因子3(SOCS3或 SOCS-3)是一種在人體內由 SOCS3基因編碼的蛋白。[1][2] 該基因編碼 STAT- 誘導的 STAT 抑制子(SSI)，也可稱為細胞因子訊息傳遞(SOCS)家族抑制子，的一個成員。 SSI 家族成員是可由細胞因子誘導的細胞因子訊息傳遞負調節因子。
功能[編輯]
SOCS3基因的表現可由多種細胞因子的誘導，包括 IL-6，IL-10，干擾素-γ(IFN-γ)。
在 IL-6，Epo，GCSF 和瘦素的信號傳導中，已發現SOCS3在各自的細胞因子受體上的結合對 SOCS3的抑制功能而言是至關重要的。
SOCS3的過表現會抑制脂肪組織和肝臟胰島素訊息傳遞，但對肌肉則不然。[3] 但是在小鼠骨骼肌中敲除 SOCS3可以保護小鼠免於肥胖相關的胰島素抵抗。[3]
由於神經醯胺合成的增加，SOCS3會增加瘦素抵抗和胰島素抵抗。[4] 因此，研究已表明去除 SOCS 基因可以預防肥胖症患者的胰島素抵抗[3]
對該小鼠中基因的同源基因的研究表明，該基因在胎兒肝臟造血和胎盤發育的負調控中發揮作用。[5]
SOCS3蛋白能與JAK2結合，抑制其活性。
相互作用[編輯]
已經證明 SOCS3可以與下列物質相互作用:
調控[編輯]
有部分證據表明 SOCS3的表現受小分子核糖核酸 miR-203的調控。[12][13]
參見[編輯]
參考文獻[編輯]
- ^ 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.
- ^ 2.0 2.1 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.
- ^ 3.0 3.1 3.2 Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity. Diabetes. 2013, 62 (1): 56–64 [2018-11-22]. PMC 3526029 可免費查閱. PMID 22961088. doi:10.2337/db12-0443. （原始內容存檔於2018-11-23）. 引用錯誤：帶有name屬性「pmid22961088」的
<ref>標籤用不同內容定義了多次 - ^ 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 可免費查閱. PMID 19435851. doi:10.1152/ajpendo.91014.2008. （原始內容存檔於2016-08-10）.
- ^ Entrez Gene: SOCS3 suppressor of cytokine signaling 3. （原始內容存檔於2010-03-07）.
- ^ 6.0 6.1 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.
- ^ 8.0 8.1 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.
擴展閱讀[編輯]
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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（頁面存檔備份，存於網際網路檔案館）.
- Zhang JG, Farley A, Nicholson SE, Willson TA, Zugaro LM, Simpson RJ, Moritz RL, Cary D, Richardson R, Hausmann G, Kile BJ, Kent SB, Alexander WS, Metcalf D, Hilton DJ, Nicola NA, Baca M (1999). "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. doi:10.1073/pnas.96.5.2071. PMC 26738. PMID 10051596（頁面存檔備份，存於網際網路檔案館）.
- 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（頁面存檔備份，存於網際網路檔案館）.
- Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, Ihle JN (1999). "SOCS3 is essential in the regulation of fetal liver erythropoiesis". Cell. 98 (5): 617–27. doi:10.1016/S0092-8674(00)80049-5. PMID 10490101（頁面存檔備份，存於網際網路檔案館）.
- Schmitz J, Weissenbach M, Haan S, Heinrich PC, Schaper F (2000). "SOCS3 exerts its inhibitory function on interleukin-6 signal transduction through the SHP2 recruitment site of gp130". J. Biol. Chem. 275 (17): 12848–56. doi:10.1074/jbc.275.17.12848. PMID 10777583（頁面存檔備份，存於網際網路檔案館）.
- Ram PA, Waxman DJ (2000). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". J. Biol. Chem. 274 (50): 35553–61. doi:10.1074/jbc.274.50.35553. PMID 10585430（頁面存檔備份，存於網際網路檔案館）.
- 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（頁面存檔備份，存於網際網路檔案館）.
- Anhuf D, Weissenbach M, Schmitz J, Sobota R, Hermanns HM, Radtke S, Linnemann S, Behrmann I, Heinrich PC, Schaper F (2000). "Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation". J. Immunol. 165 (5): 2535–43. doi:10.4049/jimmunol.165.5.2535. PMID 10946280（頁面存檔備份，存於網際網路檔案館）.
- 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（頁面存檔備份，存於網際網路檔案館）.
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