PP2A-B56α is a key determinant of cardiac protein phosphorylation and functional responses to β-adrenergic signalling

Abstract

B56α is a protein phosphatase 2 A (PP2A) regulatory subunit which modulates the heart's inotropic response to acute β-adrenergic receptor (β-AR) stimulation, although knowledge of the underlying molecular mechanisms is limited. In this study, mice deficient for B56α and wildtype controls received an intraperitoneal injection of isoproterenol (0.1 mg/kg) to activate β-AR signalling in vivo, and their hearts examined two minutes post-injection by quantitative phosphoproteomics to identify mechanisms of acute β-adrenergic signalling. We identified site- and genotype-specific phosphorylation changes on >200 proteins, including 25 hyperphosphorylated proteins harbouring a B56 binding motif as put..