Tyrosine phosphatase PTPα regulates focal adhesion remodeling through Rac1 activation

We characterized the role of protein tyrosine phosphatase (PTP)-α in focal adhesion (FA) formation and remodeling using wild-type and PTPα-deficient (PTPα−/−) cells. Compared with wild-type cells, spreading PTPα−/− fibroblasts displayed fewer leading edges and formed elongated α-actinin-enriched FA at the cell periphery. These features suggest the presence of slowly remodeling cell adhesions and were phenocopied in human fibroblasts in which PTPα was knocked down using short interfering RNA (siRNA) or in NIH-3T3 fibroblasts expressing catalytically inactive (C433S/C723S) PTPα. Fluorescence recovery after photobleaching showed slower green fluorescence protein-α-actinin recovery in the FA of PTPα−/− than wild-type cells. These alterations correlated with reduced cell spreading, adhesion, and polarization and retarded contraction of extracellular matrices in PTPα−/− fibroblasts. Activation of Rac1 and its recruitment to FA during spreading were diminished in cells expressing C433S/C723S PTPα. Rac1−/− cells also displayed abnormally elongated and peripherally distributed FA that failed to remodel. Conversely, expression of constitutively active Rac1 restored normal FA remodeling in PTPα−/− cells. We conclude that PTPα is required for remodeling of FA during cell spreading via a pathway involving Rac1.