Aliases for PRKD1 Gene
External Ids for PRKD1 Gene
Previous Symbols for PRKD1 Gene
PRKD1 is a serine/threonine kinase that regulates a variety of cellular functions, including membrane receptor signaling, transport at the Golgi, protection from oxidative stress at the mitochondria, gene transcription, and regulation of cell shape, motility, and adhesion (summary by Eiseler et al., 2009 [PubMed 19329994]).[supplied by OMIM, Nov 2010]
GeneCards Summary for PRKD1 Gene
PRKD1 (Protein Kinase D1) is a Protein Coding gene. Among its related pathways are Ras signaling pathway and Development FGFR signaling pathway. GO annotations related to this gene include identical protein binding and phospholipid binding. An important paralog of this gene is PRKD3.
UniProtKB/Swiss-Prot for PRKD1 Gene
Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin 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. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor.
The protein kinase D (PKD) family of serine/threonine protein kinases contains three members; PKD1, PKD2 and PKD2. These enzymes occupy a unique position in the signal transduction pathway initiated by diacylglycerol (DAG) and protein kinase C (PKC). PKDs are direct targets of DAG, and also lie downstream of PKC in a novel signal transduction pathway that is implicated in a variety of biological processes. Structurally, PKDs contain an N terminal cysteine-rich domain (CRD), which binds phorbol esters with high affinity and has a role in mediating PKD translocation to the plasma membrane upon activation. The PH domains have an autoregulatory phosphorylation site (PKD1 and PKD2 only) and the catalytic domains have a high degree of homology to myosin light chain and calmodulin-dependent kinases. In the inactivated state, PKD1 and PKD2 are localized mainly to the cytoplasm, whilst PKD3 is found both in the cytoplasm and nucleus. Kinase activity of these enzymes is repressed by their CRD and PH domains. PKDs are activated by a variety of stimuli including regulatory peptides, lysophosphatidic acid, thrombin, PDGF, IGF-1, oxidative stress, cholecystokinin, Gbetagamma, ATP and more. These stimuli produce a rapid generation of DAG, which induces CRD-mediated PKD translocation from the cytosol to the plasma membrane. Novel PKCs are also recruited to the plasma membrane in response to DAG generation. Novel PKCs are allosterically activated by DAG, and transphosphorylate PKDs. This stabilizes PKD in its active conformation. Activated PKD dissociates from the plasma membrane, translocates to the cytosol and subsequently to the nucleus. PKDs have been implicated in fundamental physiological processes including signal transduction, membrane trafficking, and cell survival, migration, differentiation and proliferation. PKD upregulates the ERK and Ras signaling pathways, and suppresses the JNK signaling pathway. These enzymes regulate the budding of secretory vesicles from the trans-Golgi network and promote integrin recruitment to focal adhesions. In addition, PKDs have a role in regulating apoptosis and have functions in cell survival pathways induced by oxidative stress. They also have a role in immune regulation. Despite the plethora of physiological processes PKDs are involved in, only a few direct targets are known. These include kidins220, an integral membrane protein of neuroendocrine cells, c-Jun and RIN1, a protein that associates with Ras and 14.3.3 and activates the Ras-MEK-ERK pathway.