INTERFERON ACTIVATION OF THE TRANSCRIPTION FACTOR STAT91 INVOLVES DIMERIZATION THROUGH SH2-PHOSPHOTYROSYL PEPTIDE INTERACTIONS

被引:716
作者
SHUAI, K [1 ]
HORVATH, CM [1 ]
HUANG, LHT [1 ]
QURESHI, SA [1 ]
COWBURN, D [1 ]
DARNELL, JE [1 ]
机构
[1] ROCKEFELLER UNIV, PLANT BIOCHEM LAB, NEW YORK, NY 10021 USA
关键词
D O I
10.1016/0092-8674(94)90357-3
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
Stat91 (a 91 kd protein that acts as a signal transducer and activator of transcription) is inactive in the cytoplasm of untreated cells but is activated by phosphorylation on tyrosine in response to a number of polypeptide ligands, including interferon alpha (IFN-alpha) and lFN-gamma. We report here that the inactive Stat91 in the cytoplasm of untreated cells is a monomer and that upon IFN-gamma-induced phosphorylation it forms a stable homodimer. Only the dimer is capable of binding to a specific DNA sequence directing transcription. Through dissociation and reassociation assays, we show that dimerization of Stat91 is mediated through SH2-phosphotyrosyl peptide interactions. Dimerization involving SH2 recognition of specific phosphotyrosyl peptides may well provide a prototype for interactions among family members of STAT proteins to form different transcription complexes.
引用
收藏
页码:821 / 828
页数:8
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