Activation of PKC results in improved contractile effects and Ca2+ cycling by inhibition of PP2A-B56α

Abstract

The importance of the serine-41 phosphorylation site on B56α in reducing PP2A activity was demonstrated for the first time using a transgenic mutation model. The direct activation of PKC inhibits PP2A, leading to increased phosphorylation of MyBP-C in cardiac myocytes. The increased phosphorylation of contractile proteins is influenced by the PKC-phosphoB56α-PP2A signaling cascade resulting in an improved intracellular Ca2+ handling as well as an enhanced contractility and relaxation. The PKC-mediated inhibition of PP2A also leads to a modulation of the LTCC activation and inactivation kinetics. This study highlights the importance of exploring regulatory subunits of PP2A.