STAT activation by the PDGF receptor requires juxtamembrane phosphorylation sites but not Src tyrosine kinase activation

被引:55
|
作者
Sachsenmaier, C
Sadowski, HB
Cooper, JA
机构
[1] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA
[2] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
关键词
Src; STAT; PDGF; receptor tyrosine kinase; juxtamembrane;
D O I
10.1038/sj.onc.1202694
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
Activation of the platelet-derived growth factor (PDGF) receptor tyrosine kinase induces tyrosine phosphorylation of Signal Transducer and Activator of Transcription (STAT) proteins. Since the PDGF receptor also activates the Src tyrosine kinase, it is possible that Src mediates tyrosine phosphorylation of STATs in PDGF-treated cells. Consistent with a role for Src in STAT activation, we found that a PDGF receptor juxtamembrane tyrosine residue required for Src activation is necessary and sufficient for activation of STATs 1 and 3. To test the Src requirement further, we made other mutations in the PDGF receptor juxtamembrane region that increased or decreased Src binding. In epithelial and fibroblast cells, PDGF activated STAT1, 3 and 6 in the absence of detectable binding and activation of Src. In addition, PDGF induced C-myc RNA expression and DNA synthesis even though Src was not detectably activated. The activation of MAP kinase and the induction of c-fos gene expression both correlated with STAT but not Src activation by the receptor. We conclude that juxtamembrane tyrosine phosphorylation is necessary for both Src tyrosine kinase and STAT activation by the beta PDGF receptor, but that both processes are regulated independently by this region.
引用
收藏
页码:3583 / 3592
页数:10
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