Protein kinase D: coupling extracellular stimuli to the regulation of cell physiology

Protein kinase D (PKD) mediates the actions of stimuli that promote diacylglycerol (DAG) biogenesis. By phosphorylating effectors that regulate transcription, fission and polarized transport of Golgi vesicles, as well as cell migration and survival after oxidative stress, PKDs substantially expand the range of physiological processes controlled by DAG. Dysregulated PKDs have been linked to pathologies including heart hypertrophy and cancer invasiveness. Our understanding of PKD regulation by trans-and auto-phosphorylation, as well as the sub-cellular dynamics of PKD substrate phosphorylation, have increased markedly. Selective PKD inhibitors provide new, powerful tools for elucidating the physiological roles of PKDs and potentially treating cardiac disease and cancer.