Protein-tyrosine Phosphatase PTPD1 Regulates Focal Adhesion Kinase Autophosphorylation and Cell Migration

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 ⌬1-325 ) 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.

Heme modulates intestinal epithelial cell activation: involvement of NADPHox-derived ROS signaling

“…FAK is a scaffold protein integrating the extracellular and the intracellular environments and signaling for a number of events such as migration, proliferation, and cell survival among others (7). Heme-incited NADPHox-derived ROS promotes FAK phosphorylation in a transient manner.…”

JNK Pathway-associated Phosphatase Dephosphorylates Focal Adhesion Kinase and Suppresses Cell Migration

“…Several PTPs have been implicated in regulation of FAK phosphorylation status and function. Both PTP1B and PTPD1 positively regulate FAK phosphorylation (25,26). Expression of PTP1B induces FAK phosphorylation by activating Src through dephosphorylation of Src at residue Tyr-527 (27).…”

FAK, PIP5KIγ and gelsolin cooperatively mediate force-induced expression of α-smooth muscle actin

“…The FAK signaling pathway is initiated by autophosphorylation of FAK (Carlucci et al, 2008). To study the force-dependent activation of FAK, we examined its phosphorylation at Tyr397; phosphorylation at this residue is required for full activation of FAK and for productive interactions with downstream signaling proteins (Sakurai et al, 2002;Zhao et al, 1998).…”