Protein kinase C phosphorylation of cardiac troponin I or troponin T inhibits Ca2(+)-stimulated actomyosin MgATPase activity.
Effects of troponin phosphorylation on Ca2(+)-stimulated MgATPase activity of bovine cardiac actomyosin were examined. Phosphorylation by protein kinase C of troponin I and troponin T subunits in troponin or troponin-tropomyosin complex resulted in a decreased Ca2(+)-stimulated MgATPase activity in reconstituted actomyosin, and this effect was reversed by subsequent dephosphorylation by protein phosphatase 1. It was further observed that protein kinase C phosphorylation of either troponin I or troponin T subunits led to a similar inhibition of Ca2(+)-stimulated actomyosin MgATPase activity. In all cases, EC50 values (concentrations causing 50% stimulation) for Ca2+ were not appreciably affected by troponin phosphorylation by protein kinase C. Data from phosphorylation site analysis suggests that phosphorylation of threonine 144 in troponin I and possibly threonine 280 or threonine 199 in troponin T might be important for the observed decrease of Ca2(+)-stimulated actomyosin MgATPase. It is suggested that inhibition of actomyosin MgATPase caused by protein kinase C phosphorylation of troponin I and/or troponin T represents a new mechanism that can account for in part the reported negative inotropic effect of phorbol esters on various cardiac preparations.
Noland
T A
TA
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322.
Kuo
J F
JF
D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D014336:Troponin / Q000378:metabolism*; D019210:Troponin I; D020107:Troponin T
D014336:Troponin; D019210:Troponin I; D020107:Troponin T; D000205:Actomyosin; D011493:Protein Kinase C; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium