Stress kinases and phosphatases in cardiac remodeling and heart failure

WANG Yi－bin

(Department of Anesthesiology，Physiology and Medicine，University of California，Los Angeles 90095，USA)

Intracellular signaling networks mediate specific features of cardiac remodeling in pathologically stressed hearts.Protein phosphorylation and dephosphorylation are important cell signaling events critical to myocyte hypertrophy，survival，fibrosis and contractile function.Work from our lab and others have revealed important roles for stress－activated protein kinases in different aspects of heart failure.Especially，p38 MAP kinase pathway is induced by different pathological stressors in heart.Activation of p38 MAP kinase activity contributes to hypertrophy，contractile dysfunction and extracellular matrix remodeling.Recent work from our investigation in genetic models also indicates the functional importance of p38 MAP kinase in vascular remodeling and right heart development and normal function.These data supports the functional complexity of stress－ kinase pathways in both compensatory response as well as decompensation in heart.In addition to stress kinases，our lab have also discovered a novel class of protein phosphatases involved in local and specific regulation of cardiac remodeling，including metabolic remodeling by mitochondrial targeted PP2Cm and SR calcium cycling by a SR targeted PP2Ce.These new insights revealed the signaling complexity of protein kinases and phosphatases in pathologically stressed heart.