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

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

Congreso; LI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Modulation of cell contractility and migration by integrins depends on the regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B is critical for this regulation. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that during initial cell adhesion to fibronectin and vitronectin, aggregation of β3 integrins, adaptor proteins, and activation of Src/FAK-dependent signalling occurred at small puncta localized within the lamellipodium in WT cells. These events were significantly impaired in KO cells. We established that cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype. We propose that PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway and to repress RhoA-myosin-dependent contractility at the cell periphery. These events stimulate permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration. Supported by CONICET and ANPCyT.