Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction

被引:202
作者
Kaptein, A [1 ]
Paillard, V [1 ]
Saunders, M [1 ]
机构
[1] LABS GLAXO WELLCOME, ZA COURTABOEUF, CTR RECH, F-91951 LES ULIS, FRANCE
关键词
D O I
10.1074/jbc.271.11.5961
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Interleukin-6 (IL-6) induces tyrosine phosphorylation and activation of the latent transcription factor Stat3 in HepG2 cells. Mutation of Stat3 tyrosine 705 to phenylalanine (Y705F) inhibits IL-6-induced tyrosine phosphorylation of this Stat3 mutant in transfected HepG2 cells. In cotransfections of HepG2 cells, the Stat3 mutant Y705F causes a reduction of the tyrosine phosphorylation of wild type Stat3-FLAG. Moreover, Y705F inhibits the action of endogenous Stat3 in cotransfected cells, reducing IL-6 induction of a Stat3-responsive reporter construct. Y705F therefore acts as a dominant negative mutation of Stat3.
引用
收藏
页码:5961 / 5964
页数:4
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