STAT3

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Signal transducer and activator of transcription 3 (acute-phase response factor)
信号转导及转录激活蛋白3(急性期反应因子)
PDB rendering based on 1bg1.
有效结构
PDB 直系同源检索:PDBe, RCSB
标识
代号 STAT3; APRF; HIES
扩展标识 遗传学102582 鼠基因103038 同源基因7960 ChEMBL英语ChEMBL: 4026 GeneCards: STAT3 Gene
RNA表达模式
PBB GE STAT3 208991 at tn.png
PBB GE STAT3 208992 s at tn.png
PBB GE STAT3 gnf1h01250 at tn.png
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 6774 20848
Ensembl ENSG00000168610 ENSMUSG00000004040
UniProt P40763 P42227
mRNA序列 NM_003150 NM_011486
蛋白序列 NP_003141 NP_035616
基因位置 Chr 17:
40.47 – 40.54 Mb
Chr 11:
100.89 – 100.94 Mb
PubMed查询 [1] [2]

信号转导及转录激活蛋白3英语:Signal transducer and activator of transcription 3STAT3)是一种由人类基因STAT3 编码的转录因子[1]

功能[编辑]

STAT3是STAT蛋白家族的成员。受到细胞因子和生长因子的调节,STAT3被受体相关的Janus激酶(JAK)磷酸化,形成同源或异源二聚体,并转移到细胞核,在那里它们起转录激活剂的作用。具体而言,干扰素,表皮生长因子(EGF),白细胞介素(IL-)5和IL-6等配体作用于受体,导致酪氨酸705磷酸化后,STAT3被激活。此外,STAT3可能通过丝裂原活化蛋白激酶(MAPK)[2]和c-src非受体酪氨酸激酶磷酸化丝氨酸727而激活。[3][4]STAT3介导响应细胞刺激的各种基因的表达,因此在许多细胞过程如细胞生长和细胞凋亡中起关键作用。[5]

当原肠胚形成开始时,STAT3缺陷的小鼠胚胎不能在胚胎发育第7天以后发育。[6]看来在这些发育的早期阶段,STAT3激活是胚胎干细胞(ESC)自我更新所必需的。事实上,如果STAT3通过其他方式被激活,LIF可以被省略,该LIF被提供给小鼠ESC培养物以保持其未分化状态。[7]

STAT3对于TH17辅助性T细胞的分化至关重要,TH17辅助性T细胞已涉及多种自身免疫性疾病。[8]在病毒感染期间,缺乏T细胞中STAT3的小鼠显示产生T-滤泡辅助(Tfh)细胞的能力受损,并且不能维持基于抗体的免疫性。[9]

临床意义[编辑]

在癌症中的双重作用[编辑]

相互作用[编辑]

STAT3能与下列蛋白質发生交互作用

参考文献[编辑]

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  2. ^ Tkach, Mercedes; Rosemblit, Cinthia; Rivas, Martín A.; Proietti, Cecilia J.; Díaz Flaqué, María Celeste; Mercogliano, María Florencia; Beguelin, Wendy; Maronna, Esteban; Guzmán, Pablo. p42/p44 MAPK-mediated Stat3Ser727 phosphorylation is required for progestin-induced full activation of Stat3 and breast cancer growth. Endocrine-Related Cancer. April 2013, 20 (2): 197–212. ISSN 1479-6821. PMID 23329648. doi:10.1530/ERC-12-0194. 
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  14. ^ 14.0 14.1 Yuan ZL, Guan YJ, Wang L, Wei W, Kane AB, Chin YE. Central role of the threonine residue within the p+1 loop of receptor tyrosine kinase in STAT3 constitutive phosphorylation in metastatic cancer cells. Mol. Cell. Biol. 2004, 24 (21): 9390–400. PMC 522220. PMID 15485908. doi:10.1128/MCB.24.21.9390-9400.2004. 
  15. ^ Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE. ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases. J. Biol. Chem. 1999, 274 (24): 17209–18. PMID 10358079. doi:10.1074/jbc.274.24.17209. 
  16. ^ Jung JE, Kim HS, Lee CS, Shin YJ, Kim YN, Kang GH, Kim TY, Juhnn YS, Kim SJ, Park JW, Ye SK, Chung MH. STAT3 inhibits the degradation of HIF-1alpha by pVHL-mediated ubiquitination. Exp. Mol. Med. 2008, 40 (5): 479–85. PMC 2679355. PMID 18985005. doi:10.3858/emm.2008.40.5.479. 
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延伸阅读[编辑]

  • Hoey T, Grusby MJ. STATs as mediators of cytokine-induced responses. Adv. Immunol. Advances in Immunology. 1999, 71: 145–162. ISBN 978-0-12-022471-5. PMID 9917912. doi:10.1016/S0065-2776(08)60401-0. 
  • Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene. 2002, 285 (1–2): 1–24. PMID 12039028. doi:10.1016/S0378-1119(02)00398-0. 
  • Joseph AM, Kumar M, Mitra D. Nef: "necessary and enforcing factor" in HIV infection. Curr. HIV Res. 2005, 3 (1): 87–94. PMID 15638726. doi:10.2174/1570162052773013. 
  • Inghirami G; Chiarle R; Simmons WJ; 等. New and old functions of STAT3: a pivotal target for individualized treatment of cancer. Cell Cycle. 2006, 4 (9): 1131–3. PMID 16082218.  已忽略未知参数|author-separator= (帮助)
  • Leeman RJ, Lui VW, Grandis JR. STAT3 as a therapeutic target in head and neck cancer. Expert opinion on biological therapy. 2006, 6 (3): 231–241. PMID 16503733. doi:10.1517/14712598.6.3.231. 
  • Aggarwal BB; Sethi G; Ahn KS; 等. Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: modern target but ancient solution. Ann. N. Y. Acad. Sci. 2007, 1091: 151–169. PMID 17341611. doi:10.1196/annals.1378.063.  已忽略未知参数|author-separator= (帮助)

外部链接[编辑]