PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

ANA E. GONZÁLEZ WUSENER; ÁNGELA GONZÁLEZ; FUMIHIKO NAKAMURA; CARLOS O. ARREGUI

Biology Open

The Company of Biologists

Año: 2015

Cell contractility and migration by integrins depends on preciseregulation of protein tyrosine kinase and Rho-family GTPaseactivities in specific spatiotemporal patterns. Here we show thatprotein tyrosine phosphatase PTP1B cooperates with β3 integrin toactivate the Src/FAK signalling pathway which represses RhoAmyosin-dependent contractility. Using PTP1B null (KO) cells andPTP1B reconstituted (WT) cells, we determined that early stepsfollowing cell adhesion to fibronectin and vitronectin occurred robustlyin WT cells, including aggregation of β3 integrins and adaptorproteins, and activation of Src/FAK-dependent signalling at smallpuncta in a lamellipodium. However, these events were significantlyimpaired in KO cells. We established that cytoskeletal strain and cellcontractility was highly enhanced at the periphery of KO cellscompared to WT cells. Inhibition of the Src/FAK signalling pathwayor expression of constitutive active RhoA in WT cells induced a KOcell phenotype. Conversely, expression of constitutive active Src ormyosin inhibition in KO cells restored the WT phenotype.We proposethat this novel function of PTP1B stimulates permissive conditions foradhesion and lamellipodium assembly at the protruding edge duringcell spreading and migration.