Evidence that beta3 integrin-induced Rac activation involves the calpain-dependent formation of integrin clusters that are distinct from the focal complexes and focal adhesions that form as Rac and RhoA become active.

Bialkowska, K; Kulkarni, S; Du, X; Goll, D E; Saido, T C; Fox, J E

Bialkowska, K; Kulkarni, S; Du, X; Goll, D E; Saido, T C; Fox, J E.

Afiliación

Bialkowska K; Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

J Cell Biol ; 151(3): 685-96, 2000 Oct 30.

Article en En | MEDLINE | ID: mdl-11062268

RESUMEN

Interaction of integrins with the extracellular matrix leads to transmission of signals, cytoskeletal reorganizations, and changes in cell behavior. While many signaling molecules are known to be activated within Rac-induced focal complexes or Rho-induced focal adhesions, the way in which integrin-mediated adhesion leads to activation of Rac and Rho is not known. In the present study, we identified clusters of integrin that formed upstream of Rac activation. These clusters contained a Rac-binding protein(s) and appeared to be involved in Rac activation. The integrin clusters contained calpain and calpain-cleaved beta3 integrin, while the focal complexes and focal adhesions that formed once Rac and Rho were activated did not. Moreover, the integrin clusters were dependent on calpain for their formation. In contrast, while Rac- and Rho-GTPases were dependent on calpain for their activation, formation of focal complexes and focal adhesions by constitutively active Rac or Rho, respectively, occurred even when calpain inhibitors were present. Taken together, these data are consistent with a model in which integrin-induced Rac activation requires the formation of integrin clusters. The clusters form in a calpain-dependent manner, contain calpain, calpain-cleaved integrin, and a Rac binding protein(s). Once Rac is activated, other integrin signaling complexes are formed by a calpain-independent mechanism(s).

Asunto(s)

Antígenos CD/metabolismo; Calpaína/metabolismo; Adhesiones Focales/metabolismo; Glicoproteínas de Membrana Plaquetaria/metabolismo; Proteínas de Unión al GTP rac/metabolismo; Proteína de Unión al GTP rhoA/metabolismo; Sustitución de Aminoácidos/genética; Animales; Aorta; Calpaína/antagonistas & inhibidores; Calpaína/genética; Bovinos; Adhesión Celular; Tamaño de la Célula; Extensiones de la Superficie Celular/metabolismo; Células Cultivadas; Endotelio Vascular/citología; Endotelio Vascular/enzimología; Endotelio Vascular/metabolismo; Activación Enzimática; Fibronectinas/metabolismo; Adhesiones Focales/química; Genes Dominantes/genética; Humanos; Integrina beta3; Sustancias Macromoleculares; Modelos Biológicos; Mutación/genética; Unión Proteica; Procesamiento Proteico-Postraduccional; Transducción de Señal; Vinculina/metabolismo; Vitronectina/metabolismo; Proteína de Unión al GTP rhoA/genética

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calpaína / Glicoproteínas de Membrana Plaquetaria / Antígenos CD / Proteínas de Unión al GTP rac / Proteína de Unión al GTP rhoA / Adhesiones Focales Límite: Animals / Humans Idioma: En Revista: J Cell Biol Año: 2000 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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