PRKD2

Description

The PRKD2 (protein kinase D2) is a protein-coding gene located on chromosome 19.

Serine/threonine-protein kinase D2 or PKD2 is an enzyme that in humans is encoded by the PRKD2 gene. The protein encoded by this gene belongs to the protein kinase D (PKD) family of serine/threonine protein kinases, a subfamily of protein kinase C. This kinase can be activated by phorbol esters as well as by gastrin via the cholecystokinin B receptor (CCKBR) in gastric cancer cells. It can bind to diacylglycerol (DAG) in the trans-Golgi network (TGN) and may regulate basolateral membrane protein exit from TGN. Alternative splicing results in multiple transcript variants encoding different isoforms.

PRKD2 is a serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC. It is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production. PRKD2 also plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. It may potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. In response to oxidative stress, PRKD2 is phosphorylated at Tyr-438 and Tyr-717 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B. In response to the activation of the gastrin receptor CCKBR, PRKD2 is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77. Upon TCR stimulation, PRKD2 is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation. During adaptive immune responses, PRKD2 is required in peripheral T- lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens. In epithelial cells stimulated with lysophosphatidic acid (LPA), PRKD2 is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway. During TCR-induced T- cell activation, PRKD2 interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors. In the trans-Golgi network (TGN), PRKD2 regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane. PRKD2 plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis. In the secretory pathway, PRKD2 is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN. Downstream of PRKCA, PRKD2 plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells. PRKD2 plays a regulatory role in angiogenesis and tumor growth by phosphorylating a downstream mediator CIB1 isoform 2, resulting in vascular endothelial growth factor A (VEGFA) secretion. PRKD2 interacts (via C-terminus) with LCK. PRKD2 interacts (via N-terminal AP-rich region) with CIB1 isoform 2. PRKD2 interacts (via N-terminus and zing-finger domain 1 and 2) with PRKCD in response to oxidative stress; the interaction is independent of PRKD2 tyrosine phosphorylation.

PRKD2 is also known as HSPC187, PKD2, nPKC-D2.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing