Although either RSK2 or PKD/PKCε phosphorylation only partially mimics the effects of β-adrenergic signaling, phosphorylation by both kinases mimics PKA bis-phosphorylation and abolishes the C1mC2–myosin S2Δ interaction, suggesting that the combination of both pathways might constitute a more effective heart failure treatment. This evidence concerns the gene PRKCE and heart failure.