Journal of molecular and cellular cardiology
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J. Mol. Cell. Cardiol. · Mar 2007
Glycogen synthase kinase-3beta plays a pro-apoptotic role in beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes: Role of beta1 integrins.
Beta-adrenergic receptor (beta-AR) stimulation induces apoptosis in adult rat ventricular myocytes (ARVM). beta1 integrin signaling plays a protective role in beta-AR-stimulated apoptosis. Glycogen synthase kinase-3beta (GSK-3beta), a multifunctional serine/threonine kinase, negatively regulates cardiac hypertrophy. Here we show that beta-AR stimulation (isoproterenol; 15 min) increases tyr(216) phosphorylation and GSK-3beta activity. ⋯ These data suggest that beta-AR stimulation increases GSK-3beta activity. Activation of GSK-3beta plays a pro-apoptotic role in beta-AR-stimulated apoptosis via the involvement of mitochondrial death pathway. beta1 integrins inactivate GSK-3beta and play an anti-apoptotic role via the involvement of PI3-kinase pathway. The apoptotic effects of GSK-3beta may be mediated, at least in part, via its nuclear localization and induction of pro-apoptotic genes, such as Gadd153.