Integrin-mediated tyrosine phosphorylation of SHPS-1 and its association with SHP-2 - Roles of Fak and Src family kinases

被引:133
作者
Tsuda, M
Matozaki, T
Fukunaga, K
Fujioka, Y
Imamoto, A
Noguchi, T
Takada, T
Yamao, T
Takeda, H
Ochi, F
Yamamoto, T
Kasuga, M
机构
[1] Kobe Univ, Sch Med, Dept Internal Med 2, Chuo Ku, Kobe, Hyogo 650, Japan
[2] Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA
[3] Univ Chicago, Ctr Mol Oncol, Chicago, IL 60637 USA
[4] Univ Tokyo, Inst Med Sci, Dept Oncol, Minato Ku, Tokyo 108, Japan
关键词
D O I
10.1074/jbc.273.21.13223
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
SHPS-1 is a receptor-like glycoprotein that undergoes tyrosine phosphorylation and binds SHP-2, an Src homology 2 domain containing protein tyrosine phosphatase, in response to various mitogens. Cell adhesion to extracellular matrix proteins such as fibronectin and laminin also induced the tyrosine phosphorylation of SHPS-1 and its association with SHP-2. These responses were markedly reduced in cells overexpressing the Csk kinase or in cells that lack focal adhesion kinase or the Src family kinases Src or Fyn. However, unlike Src, focal adhesion kinase did not catalyze phosphorylation of the cytoplasmic domain of SHPS-1 in vitro. Overexpression of a catalytically inactive SHP-2 markedly inhibited activation of mitogen-activated protein (MAP) kinase in response to fibronectin stimulation without affecting the extent of tyrosine phosphorylation of focal adhesion kinase or its interaction with the docking protein Grb2. Overexpression of wild-type SHPS-1 did not enhance fibronectin-induced activation of MAP kinase, These results indicate that the binding of integrins to the extracellular matrix induces tyrosine phosphorylation of SHPS-1 and its association with SHP-2, and that such phosphorylation of SHPS-1 requires both focal adhesion kinase and an Src family kinase, In addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, SHP-2 may play an important role, partly through its interaction with SHPS-1, in the activation of MAP kinase in response to the engagement of integrins by the extracellular matrix.
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页码:13223 / 13229
页数:7
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