Protein-tyrosine phosphatase PTPD1 regulates focal adhesion kinase autophosphorylation and cell migration.
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.
Carlucci
Annalisa
A
Dipartimento di Biologia e Patologia Molecolare e Cellulare, Istituto di Endocrinologia ed Oncologia Sperimentale, CNR, Facoltà di Medicina, Università Federico II, via s. Pansini, 5 80131 Napoli, Italy.
Gedressi
Chiara
C
Lignitto
Luca
L
Nezi
Luigi
L
Villa-Moruzzi
Emma
E
Avvedimento
Enrico V
EV
Gottesman
Max
M
Garbi
Corrado
C
Feliciello
Antonio
A
D000199:Actins / Q000737:chemistry; D000818:Animals; D002384:Catalysis; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism*; D015398:Signal Transduction
D000199:Actins; D005982:Glutathione Transferase; D051416:Focal Adhesion Protein-Tyrosine Kinases; C409985:PTPN21 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C522213:Ptpn21 protein, mouse