title: PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility.
abstract: Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoA-myosin-dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the 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 this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.
authors.affiliation: IIB-INTECH, Universidad Nacional de San Martín, 1650 San Martín, Buenos Aires, Argentina.
authors.forename: Ana E
authors.initials: AE
authors.lastname: González Wusener
authors.affiliation: IIB-INTECH, Universidad Nacional de San Martín, 1650 San Martín, Buenos Aires, Argentina.
authors.forename: Ángela
authors.initials: Á
authors.lastname: González
authors.affiliation: Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02445, USA.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakamura
authors.affiliation: IIB-INTECH, Universidad Nacional de San Martín, 1650 San Martín, Buenos Aires, Argentina carregui@iib.unsam.edu.ar.
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Arregui
keywords: Contractility; FAK; Integrin; Myosin; PTP1B; Src