© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Cardiac protein phosphorylation: functional and pathophysiological correlates
Department of Biochemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
* Tel.: +1 (734) 622 5170; Fax: +1 (734) 622 5987; E-mail: stephen.rapundalo@aa.wl.com
Protein phosphorylation acts a pivotal mechanism in regulating the contractile state of the heart by modulating particular levels of autonomic control on cardiac force/length relationships. Early studies of changes in cardiac protein phosphorylation focused on key components of the excitation-coupling process, namely phospholamban of the sarcoplasmic reticulum and myofibrillar troponin I. In more recent years the emphasis has shifted towards the identification of other phosphoproteins, and more importantly, the delineation of the mechanistic and signaling pathways regulating the various known phosphoproteins. In addition to cAMP- and Ca2+-calmodulin-dependent kinase processes, these have included regulation by protein kinase C and the ever-emerging family of growth factor-related kinases such as the tyrosine-, mitogen- and stress-activated protein kinases. Similarly, the role of protein dephosphorylation by protein phosphatases has been recognized as integral in modulating normal cardiac cellular function. Recent studies involving a variety of cardiovascular pathologies have demonstrated that changes in the phosphorylation states of key cardiac regulatory proteins may underlie cardiac dysfunction in disease states. The emphasis of this comprehensive review will be on discussing the role of cardiac phosphoproteins in regulating myocardial function and pathophysiology based not only on in vitro data, but more importantly, from ex vivo experiments with corroborative physiological and biochemical evidence.
KEYWORDS Phosphoproteins; Regulatory proteins; Protein kinases; Protein phosphatases; Dephosphorylation; Excitation-contraction coupling
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