imported>Ohtashinichiro：Cat-a-lot：分类间移动：从Category:基因表达到Category:基因表現

2022-11-24T12:34:25Z

Cat-a-lot：分类间移动：从Category:基因表达到Category:基因表現

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{{infobox_gene}}
'''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<ref name="1 Yamamoto 1994">{{Cite journal
| author = Yamamoto K, Quelle FW, Thierfelder WE, Kreider BL, Gilbert DJ, Jenkins NA, Copeland NG, Silvennoinen O, Ihle JN
| title = Stat4, a novel gamma interferon activation site-binding protein expressed in early myeloid differentiation
| url = https://archive.org/details/sim_molecular-and-cellular-biology_1994-07_14_7/page/4342
| journal = Molecular and cellular biology
| volume = 14
| issue = 7
| pages = 4342–4349
| year = 1994
| pmid = 8007943
| pmc = 358805
}}</ref>。在幼稚[[輔助性T細胞|CD4+ T cells]]发育为Th1细胞的过程<ref name="2 Kaplan 2005">{{cite journal|title=STAT4|journal=Immunologic Research|doi=10.1385/ir:31:3:231|url=https://link.springer.com/article/10.1385/IR:31:3:231|date=2005-04-01|volume=31|issue=3|language=en|pages=231–241|issn=0257-277X|accessdate=2018-04-03|author=Mark H. Kaplan|archive-date=2018-06-02|archive-url=https://web.archive.org/web/20180602115200/https://link.springer.com/article/10.1385%2FIR%3A31%3A3%3A231|dead-url=no}}</ref>和细胞响应[[白细胞介素-12|IL-12]]产生[[Γ-干扰素|IFN-γ]]的过程中是必需的<ref name="3 Bacon 1995">{{cite journal|url=http://www.pnas.org/cgi/doi/10.1073/pnas.92.16.7307|pages=7307–7311|title=Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes.|journal=Proceedings of the National Academy of Sciences|volume=92|issue=16|language=en|accessdate=2018-04-03|doi=10.1073/pnas.92.16.7307|author=C. M. Bacon, E. F. Petricoin, J. R. Ortaldo, R. C. Rees, A. C. Larner, J. A. Johnston, J. J. O'Shea}}</ref>。

==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<ref name="1 Yamamoto 1994"/>，[[STAT蛋白]]都有几个特定的[[结构域]]，包括[[N-末端|N-端]]互作结构域，中间的{{le|DNA结合结构域|DNA-binding domain}}，一个[[SH2结构域]]以及[[C-末端|C-端]]的转录激活结构域<ref name="4 Chang 2003">{{cite journal|title=STAT4 Requires the N-terminal Domain for Efficient Phosphorylation|date=2003-08-22|doi=10.1074/jbc.m302776200|language=en|journal=Journal of Biological Chemistry|volume=278|issue=34|url=http://www.jbc.org/content/278/34/32471|pages=32471–32477|issn=0021-9258|accessdate=2018-04-03|author=Hua-Chen Chang, Shangming Zhang, India Oldham, Lisa Naeger, Timothy Hoey, Mark H. Kaplan|archive-date=2018-06-04|archive-url=https://web.archive.org/web/20180604050325/http://www.jbc.org/content/278/34/32471|dead-url=no}}</ref>。

==表达==
STAT4 的分布仅限于[[骨髓细胞]]、[[胸腺]]和[[睾丸]]。<ref name="1 Yamamoto 1994"/> 在未激活的人类[[T细胞]]中，它的表达水平非常低，但它的产生过程会受[[植物血凝素]](PHA)的刺激而增加。<ref name="3 Bacon 1995"/>

==激活 STAT4 的细胞因子==
===IL-12===
[[白细胞介素]]IL-12由[[B细胞]]和[[抗原呈递细胞]]以异源[[二聚体]]形式产生。IL-12 与由两个不同亚基（IL12Rβ1 和 IL12Rβ2）组成的 IL-12R 结合，两链激活蛋白激酶JAK-STAT（连接蛋白-信号转导子和转录激活子）信号转导通路，随后是 STAT4 酪氨酸693的磷酸化。然后该途径诱导IFNγ产生和Th1分化。STAT4通过靶向 Runx1 和 Runx3 的启动子区域，对于促进自然杀伤 (NK) 细胞的抗病毒反应至关重要。<ref name="5 Wurster 2000">{{cite journal|url=http://www.nature.com/articles/1203485|pages=2577–2584|title=The biology of Stat4 and Stat6|journal=Oncogene|volume=19|issue=21|issn=1476-5594|date=2000/05|language=En|accessdate=2018-04-03|doi=10.1038/sj.onc.1203485|author=Andrea L Wurster, Takashi Tanaka, Michael J Grusby|archive-date=2019-02-17|archive-url=https://web.archive.org/web/20190217210903/https://www.nature.com/articles/1203485|dead-url=no}}</ref>

===IFNα 和 INFβ ===
分别由[[白细胞]]、[[成纤维细胞]]分泌的I型干扰素IFNα和IFNβ 共同调节抗病毒[[免疫]]、[[细胞增殖]]和抗肿瘤作用。在病毒感染信号通路中，IFNα 或 IFNβ 中的任一个与由 IFNAR1 和 IFNAR2 组成的 IFN 受体 (IFNAR) 结合，紧接着是 [[STAT1]]、STAT4 和 IFN [[靶基因]]的[[磷酸化]]。在[[NK细胞]]病毒感染的初始阶段，STAT1 激活被 STAT4 激活取代。
<ref>{{cite journal |author1=Kumaran Satyanarayanan, S. |author2=El Kebir, D. |author3=Soboh, S. |title=IFN-β is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation |journal=Nature Communications |date=2019-08-02 |doi=10.1038/s41467-019-10903-9 |url=https://www.nature.com/articles/s41467-019-10903-9 |access-date=2021-08-09 |archive-date=2021-08-09 |archive-url=https://web.archive.org/web/20210809092342/https://www.nature.com/articles/s41467-019-10903-9 |dead-url=no }}</ref>

===IL-23===
当暴露于革兰氏阳性/阴性细菌或病毒分子后，单核细胞、活化的树突细胞 (DC) 和巨噬细胞会刺激 IL-23 的积累。受体IL-23包含IL12β 1和IL23R亚基，其在IL-23结合促进磷酸化STAT4。在慢性炎症中，IL-23/STAT4 信号通路参与诱导 Th17 促炎性 T 辅助细胞的分化和扩增。

此外，已知其他细胞因子如 IL2、IL 27、IL35、IL18 和 IL21 亦可激活 STAT4。

==靶标基因==
STAT4可结合人类基因组中的数百个位点<ref name="6 Good 2009">{{cite journal|title=Temporal Induction Pattern of STAT4 Target Genes Defines Potential for Th1 Lineage-Specific Programming|journal=The Journal of Immunology|date=2009-09-15|doi=10.4049/jimmunol.0901411|url=http://www.jimmunol.org/content/183/6/3839|language=en|volume=183|issue=6|pages=3839–3847|issn=0022-1767|accessdate=2018-04-03|author=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|archive-date=2018-06-02|archive-url=https://web.archive.org/web/20180602021621/http://www.jimmunol.org/content/183/6/3839|dead-url=no}}</ref>，其中包括许多[[细胞因子]]（[[Γ-干扰素|IFN-γ]]、[[肿瘤坏死因子|TNF]]）、受体([[IL18R1]], [[Interleukin 12 receptor, beta 2 subunit|IL12rβ2]], [[IL18RAP]])和信号因子（[[MYD88]]）的[[启动子]]区域<ref name="6 Good 2009"/>。

==参考文献==
{{Reflist}}

==延伸阅读==
*{{cite journal | author=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. | title= A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus. | url=https://archive.org/details/sim_annals-of-the-rheumatic-diseases_2010-05_69_5/page/834 | journal=Ann Rheum Dis. | volume=69 | issue=5 | pages=834–40. | year=2010 | pmid=19762360 | doi=10.1136/ard.2009.115535}}

==外部链接==
* {{MeshName|STAT4+Transcription+Factor}}

{{Transcription factors|g4}}
{{JAK-STAT信号通路}}

{{DEFAULTSORT:Stat4}}
[[Category:基因表現]]
[[Category:免疫系统]]
[[Category:转录因子]]
[[Category:信号转导]]

STAT4 - 版本历史

imported>Ohtashinichiro：​Cat-a-lot：分类间移动：从Category:基因表达到Category:基因表現

imported>Ohtashinichiro：Cat-a-lot：分类间移动：从Category:基因表达到Category:基因表現