Load-induced focal adhesion kinase activation in the myocardium: role of stretch and contractile activity

Autor(es)

Domingos, Priscila P. ; Fonseca, Priscila M. ; Nadruz Júnior, Wilson ; Franchini, Kleber G. ^[4]

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 282, n. 2, p. H556-H564, 2002.
• Área do conhecimento: Ciências da Saúde - Medicina
• Assunto(s): Sistema cardiovascular Miocárdio Citoesqueleto

Resumo

We investigated the influence of stretch and contractile activity on load-induced activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK)1/2 in isolated rat hearts. Increases of diastolic pressure from ~0 to ~15 mmHg rapidly increased FAK tyrosine phosphorylation (maximum: 2.3-fold) and binding to c-Src (maximum: 2.8-fold) and Grb2 (maximum: 3.6-fold). This was paralleled by activation (maximum: 2.8-fold) and binding of ERK1/2 to FAK. FAK and ERK1/2 were immunolocalized at sarcolemmal sites of cardiac myocytes and in the nuclei, in the case of ERK1/2. Balloon inflation to raise ventricular pressure in hearts perfused with cardioplegic solution also activated FAK and ERK1/2. However, increases in contractile activity induced by increasing calcium concentration in the perfusate (from 0.5 to 5 mM) did not activate the FAK multicomponent signaling complex or ERK1/2 in the myocardium. These results indicate that stretch rather than contractile activity induces FAK and ERK1/2 activation in the myocardium. In addition, the activation and binding of ERK1/2 to FAK suggest that FAK drives the load-induced activation of ERK1/2. (AU)

• Processo FAPESP: 98/11403-7 - Sinalizacao celular durante aumento de tensao no coracao: implicacoes no desenvolvimento de hipertrofia cardiaca.
• Beneficiário: Kleber Gomes Franchini
• Modalidade de apoio: Auxílio à Pesquisa - Regular