Tyrosine residues within the intracellular domain of the erythropoietin receptor mediate activation of AP-1 transcription factors

被引:31
作者
Bergelson, S
Klingmüller, U
Socolovsky, M
Hsiao, JG
Lodish, HF [1 ]
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[2] MIT, Dept Biol, Cambridge, MA 02139 USA
关键词
D O I
10.1074/jbc.273.4.2396
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
Binding of erythropoietin (Epo) to the Epo receptor (EpoR) initiates a signaling cascade resulting in tyrosine phosphorylation of several proteins and induction of AP-1 transcription factor(s). While Epo is known to activate c-fos gene expression, the mechanism of AP-1 activation is unknown. Here we show that AP-1 activation by Epo requires tyrosine kinase activity and also de novo protein synthesis. Using a mutant EpoR containing no cytosolic tyrosine residues, and a set of eight mutants containing a single cytosolic tyrosine residue, we show that multiple EpoR tyrosines, thought to activate multiple intracellular signal transduction proteins, can mediate AP-1 activation. An EpoR containing only tyrosine 343 or tyrosine 464 supports a maximal level of AP-1 activation We also show that AP-1 activation does not require maximal STAT5 activation and may occur via a STAT5-independent signaling pathway.
引用
收藏
页码:2396 / 2401
页数:6
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