Protein kinase D1: a protein of emerging translational interest

Abstract

Protein kinases are of particular interest in treatment of human diseases because of their enzymatic activity and susceptibility to successful therapeutic targeting. Protein kinase D1 (PKD1), cloned from humans and mouse by two different groups and reported simultaneously in 1990s, is emerging as a protein of translational value. Accumulating evidence in the literature demonstrate that PKD1 plays a role in several cellular processes such as apoptosis, immune regulation, cell proliferation, oxidative stress signaling, adhesion and motility. PKD1 mediates cellular functions through facilitating Golgi fission and protein transport by its domain specific interaction with several membranous, cytosolic and nuclear proteins and is regulated by several molecular mechanisms including autoinhibition, subcellular localization, phosphorylation and protein cleavage. PKD1 is down regulated in advanced prostate cancer human specimens and influences cell adhesion and motility of prostate cancer cells in vitro. In addition, PKD1 plays a role in several tissues including skin, immune cells, cardiac myocytes, thymus gland, vascular smooth muscle, osteoblasts and other cancer cells. In this review, while addressing the molecular aspects of PKD1, we will also highlight the potential translational implication of PKD1 function in human diseases.