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Published online 7 April 2003. doi:10.1083/jcb.200211061
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© The Rockefeller University Press, 0021-9525/2003/4/143 $5.00
The Journal of Cell Biology, Volume 161, Number 1, 143-153

Article

 RPTP-{alpha} acts as a transducer of mechanical force on {alpha}v/ß3-integrin–cytoskeleton linkages

Götz von Wichert1, Guoying Jiang1, Ana Kostic1, Kurt De Vos1, Jan Sap2 and Michael P. Sheetz1

1 Department of Biological Sciences, Columbia University, New York, NY 10027
2 Department of Pharmacology and Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016

Address correspondence to Michael P. Sheetz, Dept. of Biological Sciences, P.O. Box 2408, Columbia University, Sherman Fairchild Center, Rm. 713, 1212 Amsterdam Ave., New York, NY 10027. Tel.: (212) 854-4857. Fax: (212) 854-6399. E-mail: ms2001{at}columbia.edu

Cell motility on ECM critically depends on the cellular response to force from the matrix. We find that force-dependent reinforcement of {alpha}v/ß3-integrin–mediated cell–matrix connections requires the receptor-like tyrosine phosphatase {alpha} (RPTP{alpha}). RPTP{alpha} colocalizes with {alpha}v-integrins at the leading edge during early spreading, and coimmunoprecipitates with {alpha}v-integrins during spreading on fibronectin and vitronectin. RPTP{alpha}-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/ß3-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 RPTP{alpha} is an early component in force-dependent signal transduction pathways leading to the assembly of focal complexes on both fibronectin and vitronectin.

Key Words: phosphatase; force; src family kinases; focal contact; mechanotransduction

* Abbreviations used in this paper: CSK, c-terminal Src kinase; FN, fibronectin; GPen, GPenGRGDSPCA; LA, laminin; MSD, mean square displacement; RPTP{alpha}, receptor-like protein tyrosine phosphatase {alpha}; SFK, Src family kinase; VN, vitronectin.


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