The JAK-STAT pathway: impact on human disease and therapeutic intervention.

The JAK-STAT pathway: impact on human disease and therapeutic intervention.
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DOI:
10.1146/annurev-med-051113-024537
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发表时间:
2015
影响因子:
10.5
通讯作者:
Laurence A
Laurence A
中科院分区:
医学1区
文献类型:
--
作者:
O'Shea JJ;Schwartz DM;Villarino AV;Gadina M;McInnes IB;Laurence A

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Janus激酶(JAK)是通过研究干扰素基因诱导而发现的信号转导激活(STAT)途径,现在被认为是多种细胞因子、干扰素、生长因子和相关分子所采用的进化上保守的信号传导途径。这一途径提供了一个优雅的,非常简单的机制,细胞外因子控制基因表达。因此,它是细胞如何感知环境信号并解释这些信号以调节细胞生长和分化的基本范式。功能相关的基因突变和多态性与多种人类疾病相关,特别是癌症和免疫相关病症。最后,靶向JAK的一类新疗法的出现证实了该途径的临床相关性。
The Janus kinase (JAK), signal transducer of activation (STAT) pathway, discovered by investigating interferon gene induction, is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. This pathway provides an elegant, and remarkably straightforward mechanism whereby extracellular factors control gene expression. It thus serves as a fundamental paradigm for how cells sense environmental cues and interpret these signals to regulate cell growth and differentiation. Functionally relevant genetic mutations and polymorphisms are relevant to a variety of human diseases, especially cancer and immune-related conditions. Finally, the clinical relevance of the pathway has been confirmed by the emergence of a new class of therapeutics that target JAKs.
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