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Protein Kinases as Drug Development Targets for Heart Disease Therapy
Institute of Cardiovascular Sciences, St. Boniface Hospital Research, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
* Author to whom correspondence should be addressed.
Received: 9 April 2010; in revised form: 3 June 2010 / Accepted: 23 June 2010 / Published: 5 July 2010
Abstract: Protein kinases are intimately integrated in different signal transduction pathways for the regulation of cardiac function in both health and disease. Protein kinase A (PKA), Ca2+-calmodulin-dependent protein kinase (CaMK), protein kinase C (PKC), phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) are not only involved in the control of subcellular activities for maintaining cardiac function, but also participate in the development of cardiac dysfunction in cardiac hypertrophy, diabetic cardiomyopathy, myocardial infarction, and heart failure. Although all these kinases serve as signal transducing proteins by phosphorylating different sites in cardiomyocytes, some of their effects are cardioprotective whereas others are detrimental. Such opposing effects of each signal transduction pathway seem to depend upon the duration and intensity of stimulus as well as the type of kinase isoform for each kinase. In view of the fact that most of these kinases are activated in heart disease and their inhibition has been shown to improve cardiac function, it is suggested that these kinases form excellent targets for drug development for therapy of heart disease.
Keywords: protein kinase A; protein kinase C; Ca2+ calmodulin protein kinase; mitogen-activated protein kinases; phosphoinositide 3-kinase
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MDPI and ACS Style
Dhalla, N.S.; Müller, A.L. Protein Kinases as Drug Development Targets for Heart Disease Therapy. Pharmaceuticals 2010, 3, 2111-2145.
Dhalla NS, Müller AL. Protein Kinases as Drug Development Targets for Heart Disease Therapy. Pharmaceuticals. 2010; 3(7):2111-2145.
Dhalla, Naranjan S.; Müller, Alison L. 2010. "Protein Kinases as Drug Development Targets for Heart Disease Therapy." Pharmaceuticals 3, no. 7: 2111-2145.