PRKD2
Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and 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, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. 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, 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, 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, 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, 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), 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, 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), 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. 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 secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN. Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells. 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. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily. Widely expressed. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: CAMK group; EC 2.7.11.13; Kinase, protein; Motility/polarity/chemotaxis; PKD family; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor)
Molecular Function: ATP binding; calcium-dependent protein kinase C activity; kinase activity; metal ion binding; nucleotide binding; protein kinase activity; protein kinase C activity; protein kinase C binding; protein serine/threonine kinase activity; transferase activity
Biological Process: adaptive immune response; angiogenesis; cell adhesion; cellular response to vascular endothelial growth factor stimulus; immune system process; intracellular signal transduction; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; phosphorylation; positive regulation of angiogenesis; positive regulation of blood vessel endothelial cell migration; positive regulation of cell adhesion; positive regulation of CREB transcription factor activity; positive regulation of DNA biosynthetic process; positive regulation of DNA-binding transcription factor activity; positive regulation of endothelial cell chemotaxis; positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway; positive regulation of endothelial cell migration; positive regulation of endothelial cell proliferation; positive regulation of ERK1 and ERK2 cascade; positive regulation of fibroblast growth factor receptor signaling pathway; positive regulation of histone deacetylase activity; positive regulation of interleukin-2 production; positive regulation of interleukin-8 production; positive regulation of intracellular signal transduction; positive regulation of NF-kappaB transcription factor activity; positive regulation of peptidyl-serine phosphorylation; positive regulation of T cell receptor signaling pathway; positive regulation of transcription by RNA polymerase II; positive regulation of vascular endothelial growth factor receptor signaling pathway; protein autophosphorylation; protein kinase D signaling; protein phosphorylation; regulation of T cell apoptotic process; T cell receptor signaling pathway; vascular endothelial growth factor receptor signaling pathway
