Another New Kinase Targets Troponin I

Abstract

See related article, pages 1091–1099 In this issue of Circulation Research , Haworth et al1 report that protein kinase D (PKD), a serine kinase, phosphorylates the cardiac thin filament protein, troponin I (TnI). These investigators performed a detailed and complete set of experiments, initially noting the association of TnI and PKD, and then mapping the sites that PKD phosphorylates, Ser22 and Ser23. PKD treatment of myocytes was further demonstrated to result in desensitization of the myofilaments to calcium and accelerated isometric crossbridge cycling.1 Why is finding an additional kinase for TnI important? TnI is a critical component of the calcium switch of striated muscle, and the cardiac specific isoform is further specialized because of the presence of an amino-terminal region containing protein kinase A (PKA) sites. Troponin (Tn) consists of three subunits including TnI, the inhibitory component, which inhibits actin-myosin interactions at diastolic calcium levels, TnC, the calcium binding subunit, and TnT, which anchors Tn to tropomyosin (Tm) but also contributes to regulation of muscle activation. During systole, a regulatory Ca2+ -binding site on TnC is occupied, increasing the affinity of TnC for TnI and lessening the interaction between TnI and actin-Tm. This results in movement of Tm-Tn on the thin filament, releasing the inhibition of actin-myosin interactions and increasing the probability of cycling of the crossbridge and muscle shortening (reviewed by Tobacman2). Studies conducted in the 1970s demonstrated TnI to be a target of …