Protein-tyrosine phosphatase PTPD1 regulates focal adhesion kinase autophosphorylation and cell migration.
Carlucci, Annalisa ; Gedressi, Chiara ; Lignitto, Luca ; et al. ; - ASI Sponsor
Apr - 2008
DOI: 10.1074/jbc.M707248200
ISSN : 0021-9258 ;
journal : The Journal of biological chemistry

Issue : 16
type: Article Journal

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.

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