JAK-STAT信号通路研究进展

摘要/Abstract

摘要： 信号通路JAK-STAT参与机体多种调节反应,在细胞因子等与其相应受体结合后激活JAK激酶,进一步活化其下游信号蛋白分子STAT,导致STAT同源或异源二聚体化,随后二聚体蛋白移位核内,与相应的靶基因启动子结合,控制目的蛋白的表达,对机体的调控起着重要作用。

关键词: 信号通路; JAK-STAT; 转导

Abstract: JAK-STAT signaling pathway involved in various of physiological and pathological responses. JAK kinases were activated after the binding of cytokines to their corresponding receptors, further phosphorylation of STATs were produced which result in homologous or heterologous dimerization, the dimeric protein then translocated into the nucleus and binding the promoters of relevant target genes for the controlling of expression of objective proteins. Consequently, the pathway plays an momentous role in the regulationg of organisms.

Key words: signaling pathway; JAK-STAT; transduce

中图分类号:

宋舟, 张立艳, 董海兵, 白换力, 陈伟, 吴帅成, 伊鹏霏, 付本懂, 申海清, 韦旭斌. JAK-STAT信号通路研究进展[J]. , 2012, 39(6): 128-132.

SONG Zhou, ZHANG Li-yan, DONG Hai-bing, BAI Huan-li, CHEN Wei, WU Shuai-cheng, YI Peng-fei, FU Ben-dong, SHEN Hai-qing, WEI Xu-bin. Advances in JAK-STAT Signaling Pathway[J]. , 2012, 39(6): 128-132.

参考文献

1 Aggarwal B B, Kunnumakkara A B, Harikumar K B, et al. Signal transducer and activator of transcription-3,inflammation ,and cancer: how intimate is the relationship[J].Ann N Y Acad Sci,2009,1171:59~76.
2 Bahia A C, Kubota M S, Tempone A J, et al.The JAK-STAT pathway controls plasmodium vivax load in early stages of anopheles aquasalis tnfection[J].PLoS Negl Trop Dis,2011,5(11):e1317.
3 Berthier C C, Zhang H Y, Schin M L, et al. Enhanced expression of Janus kinase-signal transducer and activator of transcription pathway members in human diabetic nephropathy[J].Diabetes,2009,58(2):469~477.
4 Burdeinich-Kerr R, Govindarajan D, Griffin D E. Noncytolytic clearance of sindbis virus infection from neurons by gamma interferon is dependent on JAK/STAT signaling[J].J Virol,2009,83(8):3429~3435.
5 Clevenger C V. Roles and regulation of STAT family transcription factors in human breast cancer[J].Am J Pathol,2004,165(5):1449~1460.
6 Diaz T, Navarro A, Ferrer G, et al. Lestaurtinib inhibition of the JAK/STAT signaling pathway in hodgkin lymphoma inhibits proliferation and induces apoptosis[J]. PLoS One,2011,6(4):e18856.
7 Ghoreschi K, Laurence A, O’Shea J J. Janus Kinases in immune cell signaling[J].Immunol Rev,2009,228(1):273~287.
8 Guerriero M L, Dudka A, Underhill-Day N, et al. Narrative-based computational modeling of the Gp130/JAK/STAT signaling pathway[J].BMC Syst Biol,2009,3:40.
9 Hokuto I, Ikegami M, Yoshida M, et al. STAT-3 required for pulmonary homeostasis during hyperoxia[J].J Clin Invest,2004,113(1):28~37.
10 Hornakova T, Springuel L, Devreux J, et al. Oncogenic JAK1 and JAK2-activating mutations resistant to ATP-competitive inhibitors[J]. Haematologica,2011,96(6):845~853.
11 Isomoto H, Mott J L, Kobayashi S, et al. Sustained IL-6/STAT-3 signaling in cholangiocarcinoma cells due to SOCS-3 epigenetic silencing[J].Gastroenterology,2007,132(1):384~396.
12 Isozaki T, Kasama T, Takahashi R, et al. Synergistic induction of CX3CL by TNF alpha and IFN gamma in osteoblasts from rheumatoid arthritis: involvement of NF-kappa B and STAT-1 signaling pathways[J].J Inflamm Res,2008,1:19~28.
13 Issigonis M, Tulina N, de Cuevas M, et al. JAK-STAT signal inhibition regulates competition in the Drosophila testis stem cell Niche[J].Science,2009,326(5949):153~156.
14 Ivashkiv L B,Hu X Y. Signaling by STATs[J].Arthritis Res Ther,2004,6(4):159~168.
15 Jae-Ho C, Hong S Y, ZhengY J, et al. Eupatilin inhibits gastric cancer cell growth by blocking STAT3-mediated VEGF expression[J].J Gastric Cancer,2011,11(1):16~22.
16 Jiang H, Patel P H, Kohlmaier A, et al. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut[J].Cell,2009,137(7):1343~1355.
17 Kacimi R, Giffard R G, Yenari M A. Endotoxin-activated microglia injure brain derived endothelial cells via NF-κB, JAK-STAT and JNK stress kinase pathways[J].J Inflamm,2011,8:7.
18 Kim D J, Tremblay M L, Giovanni J D. Protein tyrosine phosphatases,TC-PTP, SHP1, and SHP2, cooperate in rapid Dephosphorylation of Stat3 in keratinocytes following UVB irradiation[J]. PLoS One,2010,5(4):e10290.
19 Li W X. Canonical and non-canonical JAK-STAT signaling[J].Trends Cell Biol,2008,18(11):545~551.
20 Liu X D,Ye L L, Bai Y, et al. Activation of the JAK/STAT-1 signaling pathway by IFN-γ can down-regulate functional expression of the MHC class Ⅰ-related neonatal Fc receptor for IgG[J]. J Immunol,2008,181(1):449~463.
21 Liu Y, Li P K, Li C L, et al. Inhibition of STAT3 signaling blocks the anti-apoptotic activity of IL-6 in human liver cancer cells[J].J Biol Chem,2010,285(35):27429~27439.
22 Makki R, Meister M, Pennetier D, et al. A short receptor downregulates JAK/STAT signalling to control the Drosophila cellular immune response[J].PLoS Biol,2010,8(8):e1000441.
23 Marodi L, Goda K, Palicz A, et al. Cytokine receptor signaling in neonatal macrophages:defective STAT-1 phosphorylation in response to stimulation with IFN-γ[J].Clin Exp Immunol,2001,126(3):456~460.
24 Mitchell T J,John S. Signal transducer and activator of transcription(STAT) signaling and T-cell lymphomas[J]. Immunology, 2005,114(3):301~312.
25 Morales J K, Falanga Y T, Depcrynski A, et al. Mast cell homeostasis and the JAK-STAT pathway[J].Genes Immun, 2010, 11(8):599~608.
26 Muller P, Boutros M, Zeidler M P. Identification of JAK/STAT pathway regulators-insights from RNAi screens[J].Semin Cell Dev Biol,2008,19(4~2):360~369.
27 Pouliot P, Bergeron S, Marette A, et al. The role of protein tyrosine phosphatases in the regulation of allergic asthma:implication of TC-PTP and PTP-1B in the modulation of disease development[J].Immunology,2009,128(4):534~542.
28 Proia D A, Foley K P, Korbut T, et al. Multifaceted intervention by the Hsp90 inhibitor ganetespib (STA-9090) in cancer cells with activated JAK/STAT signaling[J]. PLoS One,2011,6(4):e18552.
29 Quaiser T,Dittrich A,Schaper F, et al. A simple work flow for biologically inspired model reduction-application to early JAK-STAT signaling[J]. BMC Syst Biol,2011,5:30.
30 Saha R N, Pahan K. Regulation of inducible nitric oxide synthase gene in glial cells[J]. Antioxid Redox Signal,2006,8(5):929~947.
31 Sahu R P, SrivastavaS K. The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate[J].J Natl Cancer Inst,2009,101(3):176~193.
32 Schindler C, Plumlee C. Inteferons pen the JAK-STAT pathway[J].Semin Cell Dev Biol,2008,19(4):311~318.
33 Sehgal P. Paradigm shifts in the cell biology of STAT signaling[J].Semin Cell Dev Biol,2008,19(4):329~340.
34 Souza-Neto J A, Sim S, Dimopoulos G. An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense[J].Proc Natl Acad Sci USA,2009,106(42):17841~17846.
35 Takaoka A, Mitani Y, Suemori H, et al. Cross talk between interferon-γ and –α/β signaling components in caveolar membrane domains[J].Science,2000,288:2357~2360.
36 Takemoto S, Mulloy J C, Cereseto A, et al. Proliferation of adult T cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins[J].Proc Natl Acad Sci U S A,1997,94(25):13897~13902.
37 Toth K G, McKay B R, de Lisio M, et al. IL-6 induced STAT3 signalling is associated with the proliferation of human muscle satellite cells following acute muscle damage[J]. PLoS One,2011,6(3):e17392.
38 Wang Y H, Huang M L. Organogenesis and tumorigenesis:Insight from the JAK/STAT pathway in the Drosophila eye[J].Dev Dyn,2010,239(10):2522~2533.
39 Wawersik M, Milutinovich A, Casper A L, et al. Somatic control of germline sexual development is mediated by the JAK/STAT pathway[J].Nature,2005,436(7050):563~567.
40 Xu D, Qu C K. Protein tyrosine phosphatases in the JAK/STAT pathway[J]. Front Biosci,2008,13:4925~4932.

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