Protein-tyrosine phosphatase PTPD1 regulates focal adhesion kinase autophosphorylation and cell migration

J Biol Chem. 2008 Apr 18;283(16):10919-29. doi: 10.1074/jbc.M707248200. Epub 2008 Jan 26.

Abstract

PTPD1 is a cytosolic nonreceptor tyrosine phosphatase and a positive regulator of the Src-epidermal growth factor transduction pathway. We show that PTPD1 localizes along actin filaments and at adhesion plaques. PTPD1 forms a stable complex via distinct molecular modules with actin, Src tyrosine kinase, and focal adhesion kinase (FAK), a scaffold protein kinase enriched at adhesion plaques. Overexpression of PTPD1 promoted cell scattering and migration, short hairpin RNA-mediated silencing of endogenous PTPD1, or expression of PTPD1 mutants lacking either catalytic activity (PTPD1(C1108S)) or the FERM domain (PTPD1(Delta1-325)) significantly reduced cell motility. PTPD1 and Src catalytic activities were both required for epidermal growth factor-induced FAK autophosphorylation at its active site and for downstream propagation of ERK1/2 signaling. Our findings demonstrate that PTPD1 is a component of a multivalent scaffold complex nucleated by FAK at specific intracellular sites. By modulating Src-FAK signaling at adhesion sites, PTPD1 promotes the cytoskeleton events that induce cell adhesion and migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Animals
  • Catalysis
  • Cell Adhesion
  • Cytoskeleton / metabolism
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism
  • Glutathione Transferase / metabolism
  • Humans
  • Mice
  • Models, Biological
  • NIH 3T3 Cells
  • Phosphorylation
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism*
  • Signal Transduction

Substances

  • Actins
  • Glutathione Transferase
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTPN21 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Ptpn21 protein, mouse