STAT4

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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 鼠类
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 [1] [2]

STAT4转录因子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]

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. ^ Kaplan MH. STAT4: A Critical Regulator of Inflammation in Vivo. Immunologic Research. 2005, 31 (3): 231–242. doi:10.1385/IR:31:3:231. PMID 15888914. 
  3. ^ 3.0 3.1 Bacon CM. Interleukin 12 Induces Tyrosine Phosphorylation and Activation of STAT4 in Human Lymphocytes. Proceedings of the National Academy of Sciences. 1995, 92 (16): 7307–7311. doi:10.1073/pnas.92.16.7307. 
  4. ^ Chang HC, Zhang S, Oldham I, Naeger L, Hoey T, Kaplan MH. STAT4 Requires the N-terminal Domain for Efficient Phosphorylation. Journal of Biological Chemistry. 2003, 278 (34): 32471–32477. doi:10.1074/jbc.M302776200. PMID 12805384. 
  5. ^ Wurster AL, Tanaka T, Grusby MJ. The biology of Stat4 and Stat6. Oncogene. 2000, 19 (21): 2577–2584. doi:10.1038/sj.onc.1203485. PMID 10851056. 
  6. ^ 6.0 6.1 Good SR, Thieu VT, Mathur AN, Yu Q, Stritesky GL, Yeh N, O'Malley JT, Perumal NB, Kaplan MH. Temporal Induction Pattern of STAT4 Target Genes Defines Potential for Th1 Lineage-Specific Programming. The Journal of Immunology. 2009, 183 (6): 3839–3847. doi:10.4049/jimmunol.0901411. PMC 2748807. PMID 19710469. 

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. doi:10.1136/ard.2009.115535. PMID 19762360. 

外部链接[编辑]