Critical role of PTP1B in transient integrin-mediated repression of myosin activity

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

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Integrin-mediated cell adhesion regulates the activity of protein tyrosine kinases and Rho GTPases in specific spatiotemporal patterns. In the current study, we show that protein tyrosine phosphatase PTP1B is critical for this regulation. PTP1B is required for an early and transient β3 integrin-mediated activation of the Src/FAK signaling pathway. During initial cell adhesion to fibronectin and vitronectin, aggregation of β3 integrin, paxillin, phospho-paxillin, and activated Src/FAK occurs at small puncta localized within the lamellipodium. All these structural and signaling hallmarks were significantly reduced in PTP1B null (KO) cells compared to PTP1B reconstituted (WT) cells. Inhibition of Src/FAK signaling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression in KO cells of constitutive active Src, or incubation with the myosin inhibitor blebbistatin, rescued the WT cell phenotype. We propose a model in which PTP1B cooperates with β3 integrins to activate Src/FAK signaling pathway, transiently repressing myosin-dependent contractility at the cell periphery. These events promote the stability of cell-matrix adhesions and the lamellipodium required for cell spreading. Supported by CONICET and ANPCyT.