A recently discovered cardiac-specific regulatory variant for PRKCA (rs9909004) was independently associated with a decreased risk for all-cause mortality in patients with HF.
Finally, PKC and non-muscle myosin are upregulated at the costameres in heart disease, indicating aberrant mechanosensing as a contributing factor to long-term remodeling and heart failure.
The minor C allele is associated with both decreased PRKCA mRNA expression and decreased risk of phenotypes characteristic of heart failure in GWAS analyses (QT interval p = 3.0 × 10<sup>-14</sup>).
Activation of the cAMP/Epac/PKCα pathway protected the heart against cytokine-induced cardiac dysfunction, suggesting a new role of catecholamine signaling in compensating for cardiac dysfunction in heart failure.
Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure.
Proline-rich tyrosine kinase 2 (Pyk2) is a nonreceptor protein kinase regulated by intracellular Ca(2+), CaMK, and PKC and can be activated by different stress signals involved in heart failure.
Augmented protein kinase C-alpha-induced myofilament protein phosphorylation contributes to myofilament dysfunction in experimental congestive heart failure.