Regulation of Protein Kinase D1 Activity

摘要: Protein kinase D1 (PKD1) is a stress-activated serine/threonine that plays vital role in various physiologically important biological processes, including cell growth, apoptosis, adhesion, motility, and angiogenesis. Dysregulated PKD1 expression also contributes to the pathogenesis of certain cancers cardiovascular disorders. Studies date have focused primarily on canonical membrane-delimited pathway for activation by G protein-coupled receptors or peptide growth factors. Here, agonist-dependent increases diacylglycerol accumulation lead protein C (PKC) PKC-dependent phosphorylation at two highly conserved serine residues loop; this modification catalytic activity, as assessed autophosphorylation consensus motif extreme terminus. However, recent studies expose additional controls consequences loop C-terminal well reactions trans-phosphorylations (by PKC other cellular enzymes) contribute spatiotemporal control signaling cells. This review focuses multisite phosphorylations are known predicted influence activity may docking interactions with scaffolds trafficking microdomains subcellular compartments. These modifications represent novel targets development PKD1-directed pharmaceuticals treatment