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Rho and Rho-associated kinase modulate the tyrosine kinase PYK2 in T-cells through regulation of the activity of the integrin LFA-1

AuthorsRodríguez-Fernández, José Luis ; Sánchez-Martín, Lorena; Rey, Mercedes; Vicente, Miguel; Narumiya, Shuh; Teixidó, Joaquín ; Sánchez-Madrid, Francisco; Cabañas, Carlos
Issue Date6-Aug-2001
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationThe Journal of Biological Chemistry 276, 40518-40527 (2001)
AbstractWe have examined the role of the small GTPase Rho and its downstream effector, the Rho-associated kinase (ROCK), in the control of the adhesive and signaling function of the lymphocyte function-associated antigen-1(LFA-1) integrin in human T-lymphocytes. Inhibition of Rho (either by treatment with C3-exoenzyme or transfection with a dominant-negative form of Rho (N19Rho)) or ROCK (by treatment with Y-27632) results in the following:(a) partial disorganization and aggregation of cortical filamentous actin (F-actin); (b) induction of LFA-1- mediated cellular adhesion to the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1) through a mechanism involving clustering of LFA-1 molecules, rather than alterations in the level of expression or in the affinity state of this integrin; and (c) induction of cellular polarization and activation of the tyrosine kinase PYK2.Transfection of T-cells with a constitutively active form of Rho (V14Rho) blocks the clustering of LFA-1 on the membrane and the LFA-1-mediated activation of PYK2. Importantly, the activation of PYK2 caused by inhibition of Rho or ROCK takes place only when the T-cells are plated onto ICAM-1 but not when they are either prevented from interacting with ICAM-1 with anti-LFA-1 blocking antibodies or when they are plated on the nonspecific poly-Llysine substrate. These results indicate that the small GTPase Rho regulates the tyrosine kinase PYK2 in T-cells through the F-actin-mediated control of the activity of the integrin LFA-1. These findings represent a novel paradigm for the regulation of the activity of a cytoplasmic tyrosine kinase by the small GTPase Rho.
Description10 p.-9 fig.
Publisher version (URL)http://dx.doi.org/ 10.1074/jbc.M102896200
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