Gravin‐mediated PKC signaling in heart (LB571)

Abstract

Gravin is an A‐Kinase Anchoring Protein (AKAP) that scaffolds protein kinase A (PKA), protein kinase C (PKC), phosphatase 2B, β2‐adrenergic receptors to specific subcellular compartments. Studies show that scaffolding of PKC by gravin decreases PKC activity due to sequestration. Also, PKC is involved in the translocation and distribution of gravin. Our goal is to study the role of gravin in PKC signaling in the heart. Basal PKC activity in the cytosolic fractions of the homogenized hearts was found to be greater in gravin truncated (t/t) mice as compared to wild type (WT). This correlation was preserved following stimulation of the samples with a PKC activator, PMA (Phorbol 12‐myristate 13‐acetate). However, no change was observed in the extent of PKC substrate phosphorylation between these groups. It supports previous studies that PKC scaffolding by gravin decreases PKC activity. The next step is to study the effect of PKC on gravin translocation in cardiomyocytes using PKC activator PMA and inhibitor chelerythrine. We expect to see increased translocation of gravin to cytosol after PKC activation. These studies will help us better understand the functional significance of the role of gravin in PKC signaling.Grant Funding Source: R01HL085487