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STAT4

位於2號人類染色體的基因

结构编辑

人类和鼠类的STAT4基因都位于STAT1基因的附近,这一点暗示了这两个基因由基因重複而来[1]STAT蛋白都有几个特定的结构域,包括N-端互作结构域,中间的DNA结合结构域英语DNA-binding domain,一个SH2结构域以及C-端的转录激活结构域[4]

表达编辑

Distribution of STAT4 is restricted to myeloid cells, thymus and testis.[1] In resting human T cells it is expressed at very low levels, but its production is amplified by PHA stimulation.[3]

激活编辑

Two chains of IL-12 receptor form heterodimer after IL-12 binding and activate the receptor associated JAK kinases, termed JAK2 and TYK2. Stat4 is phosphorylated by these tyrosine kinases, homodimerizes via its SH2 domain and translocates into nucleus to activate gene transcription.[5]

靶标基因编辑

STAT4 binds to hundreds of sites in the genome,[6] among others to the promoters of genes for cytokines (IFN-γ, TNF), receptors (IL18R1, IL12rβ2, IL18RAP), and signaling factors (MYD88).[6]

参考文献编辑

  1. ^ 1.0 1.1 1.2 Yamamoto K, Quelle FW, Thierfelder WE, Kreider BL, Gilbert DJ, Jenkins NA, Copeland NG, Silvennoinen O, Ihle JN. Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation. Molecular and cellular biology. 1994, 14 (7): 4342–4349. PMC 358805. PMID 8007943. 
  2. ^ Mark H. Kaplan. STAT4. Immunologic Research. 2005-04-01, 31 (3): 231–241 [2018-04-03]. ISSN 0257-277X. doi:10.1385/ir:31:3:231 (英语). 
  3. ^ 3.0 3.1 C. M. Bacon, E. F. Petricoin, J. R. Ortaldo, R. C. Rees, A. C. Larner, J. A. Johnston, J. J. O'Shea. Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes.. Proceedings of the National Academy of Sciences: 7307–7311. [2018-04-03]. doi:10.1073/pnas.92.16.7307 (英语). 
  4. ^ Hua-Chen Chang, Shangming Zhang, India Oldham, Lisa Naeger, Timothy Hoey, Mark H. Kaplan. STAT4 Requires the N-terminal Domain for Efficient Phosphorylation. Journal of Biological Chemistry. 2003-08-22, 278 (34): 32471–32477 [2018-04-03]. ISSN 0021-9258. doi:10.1074/jbc.m302776200 (英语). 
  5. ^ Andrea L Wurster, Takashi Tanaka, Michael J Grusby. The biology of Stat4 and Stat6. Oncogene. 2000/05, 19 (21): 2577–2584 [2018-04-03]. ISSN 1476-5594. doi:10.1038/sj.onc.1203485 (英语). 
  6. ^ 6.0 6.1 Seth R. Good, Vivian T. Thieu, Anubhav N. Mathur, Qing Yu, Gretta L. Stritesky, Norman Yeh, John T. O'Malley, Narayanan B. Perumal, Mark H. Kaplan. Temporal Induction Pattern of STAT4 Target Genes Defines Potential for Th1 Lineage-Specific Programming. The Journal of Immunology. 2009-09-15, 183 (6): 3839–3847 [2018-04-03]. ISSN 0022-1767. doi:10.4049/jimmunol.0901411 (英语). 

延伸阅读编辑

  • Svenungsson E, Gustafsson J, Leonard D, Sandling J, Gunnarsson I, Nordmark G, Jönsen A, Bengtsson AA, Sturfelt G, Rantapää-Dahlqvist S, Elvin K, Sundin U, Garnier S, Simard JF, Sigurdsson S, Padyukov L, Syvänen AC, Rönnblom L. A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus.. Ann Rheum Dis. 2010, 69 (5): 834–40. PMID 19762360. doi:10.1136/ard.2009.115535. 

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