STAT4：修订间差异

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
基因本体论描述
分子功能	· sequence-specific DNA binding transcription factor activity; · signal transducer activity; · calcium ion binding; · sequence-specific DNA binding;
细胞成分	· nucleus; · nucleolus; · cytoplasm;
生物过程	· transcription, DNA-dependent; · protein phosphorylation; · JAK-STAT cascade; · cell proliferation; · cytokine-mediated signaling pathway; · positive regulation of transcription from RNA polymerase II promoter;
	Sources: Amigo / QuickGO
直系同源体
	查; 论; 编;

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2021年9月11日 (六) 02:22的版本

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]

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（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

STAT4 的分布仅限于骨髓细胞、胸腺和睾丸。^[1] 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。^[3]

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。^[5]

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。 ^[6]

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 binds to hundreds of sites in the genome,^[7] among others to the promoters of genes for cytokines (IFN-γ, TNF), receptors (IL18R1, IL12rβ2, IL18RAP), and signaling factors (MYD88).^[7]

参考文献

^ ^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.
^ 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. （原始内容存档于2018-06-02）（英语）.
^ ^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）.
^ 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. （原始内容存档于2018-06-04）（英语）.
^ 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. （原始内容存档于2019-02-17）（英语）. 请检查|date=中的日期值 (帮助)
^ Kumaran Satyanarayanan, S.; El Kebir, D.; Soboh, S. IFN-β is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation. Nature Communications. 2019-08-02. doi:10.1038/s41467-019-10903-9.
^ ^7.0 ^7.1 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. （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. 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.

外部链接

醫學主題詞表（MeSH）：STAT4+Transcription+Factor

[1_Yamamoto_1994-1] 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_2005-2] 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. （原始内容存档于2018-06-02）（英语）.

[3_Bacon_1995-3] 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_Chang_2003-4] 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. （原始内容存档于2018-06-04）（英语）.

[5_Wurster_2000-5] 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. （原始内容存档于2019-02-17）（英语）. 请检查|date=中的日期值 (帮助)

[6] Kumaran Satyanarayanan, S.; El Kebir, D.; Soboh, S. IFN-β is a macrophage-derived effector cytokine facilitating the resolution of bacterial inflammation. Nature Communications. 2019-08-02. doi:10.1038/s41467-019-10903-9.

[6_Good_2009-7] 7.0 ^7.1 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. （原始内容存档于2018-06-02）（英语）.

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@@ 第1行： / 第1行： @@
 {{PBB|geneid=6775}}
+'''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
-'''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 pmid|8007943|noedit}}</ref>。 It is required for the development of Th1 cells from naive [[T helper cell|CD4+ T cells]]<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> and [[Interferon-gamma|IFN-γ]] production in response to [[Interleukin 12|IL-12]].<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>
+| 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
+| journal = Molecular and cellular biology
+| volume = 14
+| issue = 7
+| pages = 4342–4349
+| year = 1994
+| pmid = 8007943
+| pmc = 358805
+}}</ref>。 It is required for the development of Th1 cells from naive [[T helper cell|CD4+ T cells]]<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> and [[Interferon-gamma|IFN-γ]] production in response to [[Interleukin 12|IL-12]].<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==