In vitro activation of Stat3 by epidermal growth factor receptor kinase

被引:176
作者
Park, OK
Schaefer, TS
Nathans, D
机构
[1] JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205
[2] JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205
关键词
signal transduction; growth factors; cytokines; JAK proteins;
D O I
10.1073/pnas.93.24.13704
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Stat proteins are SH2 domain-containing transcription factors that are activated in cells by various cytokines and growth factors, In the case of cytokines whose receptors lack protein kinase activity, phosphorylation-activation is mediated by members of the JAK family of tyrosine protein kinases, In the case of growth factors whose receptors have intrinsic tyrosine protein kinase activity, it is thought that Stat proteins can be activated either directly by the receptor or indirectly through JAK proteins, To test the possibility of direct activation, we have used purified Stat3 alpha, Stat3 beta, and epidermal growth factor receptor kinase produced in recombinant baculovirus-infected Sf9 insect cells, The Stat proteins formed a stable complex with the receptor kinase, and they were phosphorylated on tyrosine by the receptor kinase and activated for binding to DNA, properties shared with Stat proteins purified from Sf9 cells coexpressing JAK1 or JAK2, Both JAK-phosphorylated Stat3 beta and Stat3 beta phosphorylated irt vitro by the receptor kinase were 20-50 times more active on a molar basis for DNA binding than phosphorylated Stat3 alpha. We conclude that Stat3 isoforms can be directly phosphorylated and thereby activated in vitro by the epidermal growth factor receptor kinase.
引用
收藏
页码:13704 / 13708
页数:5
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