PKCζ interacts with STAT3 and promotes its activation in cardiomyocyte hypertrophy

PKCζ (protein kinase C zeta) promotes STAT3 activation during cardiomyocyte hypertrophy. In a neonatal rat cardiomyocyte hypertrophic model induced by phenylephrine (PE), both phosphorylated PKCζ and phosphorylated STAT3 increase, indicating activation of the two signaling nodes. Overexpressing PKCζ raises hypertrophic markers atrial natriuretic factor (ANF) and brain natriuretic polypeptide (BNP) and increases cell surface area, while silencing PKCζ reduces PE-induced hypertrophy. Mechanistically, PKCζ and STAT3 interact in cardiomyocytes, and PKCζ overexpression increases STAT3 phosphorylation at Ser727 and Tyr705, drives STAT3 into the nucleus, and boosts STAT3 downstream gene expression (including c-fos and angiotensinogen). PKCζ knockdown prevents PE-induced STAT3 activation, nuclear translocation, and transcriptional effects, suggesting that targeting PKCζ-STAT3 signaling could have therapeutic value for cardiac hypertrophy.