期刊
JOURNAL OF CELL BIOLOGY
卷 161, 期 1, 页码 143-153出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200211061
关键词
phosphatase; force; Src family kinases; focal contact; mechanotransduction
类别
Cell motility on ECM critically depends on the cellular response to force from the matrix. We find that force-dependent reinforcement of alpha(v)/beta(3)-integrin-mediated cell-matrix connections requires the receptorlike tyrosine phosphatase alpha (RPTPalpha). RPTPalpha colocalizes with alpha(v)-integrins at the leading edge during early spreading, and coimmunoprecipitates with alpha(v)-integrins during spreading on fibronectin and vitronectin. RPTPalpha-dependent activation of Src family kinases, in particular activation of Fyn, is required for the force-dependent formation of focal complexes and strengthening of alpha(v)/beta(3)-integrin-cytoskeleton connections during the initial phase of ECM contact. These observations indicate that Src family kinases have distinct functions during adhesion site assembly, and that RPTPalpha is an early component in force-dependent signal transduction pathways leading to the assembly of focal complexes on both fibronectin and vitronectin.
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