Regulation of cardiac contractile function by troponin I phosphorylation.
Cardiac troponin I (cTnI) is a key regulatory protein in cardiac muscle contraction and relaxation, linking Ca(2+)-troponin C binding with activation of crossbridge reactions with the thin filament. In recent years, it has become increasingly apparent that myofilament properties as well as changes in intracellular Ca(2+) have a major role in the dynamic modulation of contractile function. The phosphorylation of specific serine and threonine residues on cTnI by several different kinases represents a major physiological mechanism for alteration of myofilament properties. Furthermore, altered thin filament function plays an important role in the contractile dysfunction associated with heart failure. Modification of cTnI by protein kinases A and C has been extensively studied with especially useful information deriving from (a) in vitro studies in reconstituted detergent-skinned fibre bundles in which endogenous cTnI was replaced with various targeted cTnI mutants and (b) transgenic animals in which endogenous cTnI was similarly manipulated through overexpression of cardiomyocyte-targeted cTnI mutants. cTnI may also be specifically modified by protein kinase G, p21-activated kinases and by dephosphorylation. This review focuses on recent advances in understanding the mechanisms of cTnI modification by these kinases and the consequent functional effects both under physiological conditions and in pathophysiological settings.
Layland
Joanne
J
Cardiovascular Division, King's College, London SE5 9PJ, UK.
Solaro
R John
RJ
Shah
Ajay M
AM
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism*; D054462:p21-Activated Kinases
D019210:Troponin I; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D002118:Calcium