期刊
JOURNAL OF CELL BIOLOGY
卷 162, 期 2, 页码 281-291出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200212141
关键词
integrin; adhesion; focal adhesion kinase; Src; extracellular matrix
类别
资金
- NCI NIH HHS [P01 CA040042, R37 CA029243, CA 80606, CA 29243, R01 CA029243, CA 40042] Funding Source: Medline
Activation of the Ras-MAPK signal transduction pathway is necessary for biological responses both to growth factors and ECM. Here, we provide evidence that phosphorylation of S298 of MAPK kinase 1 (MEK1) by p21-activated kinase (PAK) is a site of convergence for integrin and growth factor signaling. We find that adhesion to fibronectin induces PAK1-dependent phosphorylation of MEK1 on S298 and that this phosphorylation is necessary for efficient activation of MEK1 and subsequent MAPK activation. The rapid and efficient activation of MEK and phosphorylation on S298 induced by cell adhesion to fibronectin is influenced by FAK and Src signaling and is paralleled by localization of phospho-S298 MEK1 and phospho-MAPK staining in peripheral membrane-proximal adhesion structures. We propose that FAK/Src-dependent, PAK1-mediated phosphorylation of MEK1 on S298 is central to the organization and localization of active Raf-MEK1-MAPK signaling complexes, and that formation of such complexes contributes to the adhesion dependence of growth factor signaling to MAPK.
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