RPTP-α acts as a transducer of mechanical force on αv3-integrin-cytoskeleton linkages

G̈otz Von Wichert, Guoying Jiang, Ana Kostic, Kurt De Vos, Jan Sap, Michael P. Sheetz

Research output: Contribution to journalArticle

173 Scopus citations

Abstract

Cell motility on ECM critically depends on the cellular response to force from the matrix. We find that force-dependent reinforcement of αv3-integrin-mediated cell-matrix connections requires the receptor-like tyrosine phosphatase α (RPTPα). RPTPα colocalizes with αv-integrins at the leading edge during early spreading, and coimmunoprecipitates with αv-integrins during spreading on fibronectin and vitronectin. RPTPα-dependent activation of Src family kinases, in particular activation of Fyn, is required for the force-dependent formation of focal complexes and strengthening of αv3-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 RPTPα is an early component in force-dependent signal transduction pathways leading to the assembly of focal complexes on both fibronectin and vitronectin.

Original languageEnglish (US)
Pages (from-to)143-153
Number of pages11
JournalJournal of Cell Biology
Volume161
Issue number1
DOIs
StatePublished - Apr 14 2003

Keywords

  • Focal contact
  • Force
  • Mechanotransduction
  • Phosphatase
  • src family kinases

ASJC Scopus subject areas

  • Cell Biology

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