STAT4

STAT4是转录因子中信号转导及转录激活蛋白（STAT蛋白）家族的一员[1]。 It is required for the development of Th1 cells from naive CD4+ T cells[2] and IFN-γ production in response to IL-12.[3]

Signal transducer and activator of transcription 4
信号转导及转录激活蛋白4
标识
代号 STAT4; SLEB11
扩展标识 遗传学：600558 同源基因：20679 GeneCards: STAT4 Gene
直系同源体
物种 人类 小鼠
Entrez 6775 20849
Ensembl ENSG00000138378 ENSMUSG00000062939
UniProt Q14765 P42228
mRNA序列 NM_001243835 NM_011487
蛋白序列 NP_001230764 NP_035617
基因位置 Chr 2:
191.89 – 192.02 Mb		 Chr 1:
51.99 – 52.11 Mb
PubMed查询

结构

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，一个SH2结构域以及C-端的转录激活结构域[4]。

表达

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

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

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
  1. Yamamoto K, Quelle FW, Thierfelder WE, Kreider BL, Gilbert DJ, Jenkins NA, Copeland NG, Silvennoinen O, Ihle JN. . Molecular and cellular biology. 1994, 14 (7): 4342–4349. PMC 358805. PMID 8007943.
  2. Mark H. Kaplan. . Immunologic Research. 2005-04-01, 31 (3): 231–241 [2018-04-03]. ISSN 0257-277X. doi:10.1385/ir:31:3:231. （原始内容存档于2018-06-02） （英语）.
  3. C. M. Bacon, E. F. Petricoin, J. R. Ortaldo, R. C. Rees, A. C. Larner, J. A. Johnston, J. J. O'Shea. . 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. . Journal of Biological Chemistry. 2003-08-22, 278 (34): 32471–32477 [2018-04-03]. ISSN 0021-9258. doi:10.1074/jbc.m302776200. （原始内容存档于2018-06-04） （英语）.
  5. Andrea L Wurster, Takashi Tanaka, Michael J Grusby. . Oncogene. 2000/05, 19 (21): 2577–2584 [2018-04-03]. ISSN 1476-5594. doi:10.1038/sj.onc.1203485. （原始内容存档于2019-02-17） （英语）.
  6. 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. . The Journal of Immunology. 2009-09-15, 183 (6): 3839–3847 [2018-04-03]. ISSN 0022-1767. doi:10.4049/jimmunol.0901411. （原始内容存档于2018-06-02） （英语）.

延伸阅读
  • 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. . Ann Rheum Dis. 2010, 69 (5): 834–40. PMID 19762360. doi:10.1136/ard.2009.115535.

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