Phorbol 12-Myristate 13-Acetate-dependent Protein Kinase Cδ-Tyr311 Phosphorylation in Cardiomyocyte Caveolae

摘要: Protein kinase Cδ (PKCδ) activation is generally attributed to lipid cofactor-dependent allosteric mechanisms at membranes. However, recent studies indicate that PKCδ also dynamically regulated through tyrosine phosphorylation in H2O2- and phorbol 12-myristate 13-acetate (PMA)-treated cardiomyocytes. H2O2 activates Src related Src-family kinases (SFKs), which function as dual PKCδ-Tyr311 -Tyr332 vitro contribute H2O2-dependent PKCδ-Tyr311/Tyr332 cardiomyocytes mouse embryo fibroblasts. defective SYF cells (deficient SFKs) restored by re-expression. PMA promotes phosphorylation, but this not associated with SFK or PKCδ-Tyr332 phosphorylation. Rather, increases delivering SFK-enriched caveolae. Cyclodextrin treatment disrupts caveolae blocks PMA-dependent without blocking The enzyme acts a increasing Tyr332 PMA-treated uncertain. Although assays implicate c-Abl selective kinase, persists treated the inhibitor ST1571 detected caveolae; these results effectively exclude c-Abl-dependent process. Finally, we show 1,2-dioleoyl-sn-glycerol mimics effect of drive increase whereas G protein-coupled receptor agonists such norepinephrine endothelin-1 do not. These suggest accumulation activate exclusively non-caveolae Collectively, identify stimulus-specific localization could be targeted for therapeutic advantage.