PRKD1 - Serine/threonine-protein kinase D1 - human protein (Function)
 
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PRKD1 »  Serine/threonine-protein kinase D1   [ EC 2.7.11.13 ]
 
Protein also known as:  Protein kinase C mu type.
Gene name:  PRKD1
Entry whose protein(s) existence is based on evidence at protein level
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1 164 1
GENE REF ISO

Function

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Overview 
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.  
10
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Identical protein bindingdefinition[GO:0042802]  
1
  • IPIIntAct
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
6
  • IPIIntAct
  • IPIUniProtKB
Protein kinase C activitydefinition[GO:0004697]  
  • IEAEC 2 GO
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDABHF-UCL
  • TASUniProtKB
GO biological process 
Angiogenesisdefinition[GO:0001525]  
  • IEAUniProtKB KW
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
Cell proliferationdefinition[GO:0008283]  
1
  • TASPINC
Cellular response to oxidative stressdefinition[GO:0034599]  
1
  • IDAUniProtKB
Cellular response to vascular endothelial growth factor stimulusdefinition[GO:0035924]  
4
  • IGIBHF-UCL
  • IMPUniProtKB
Golgi organizationdefinition[GO:0007030]  
1
  • IMPUniProtKB
Golgi vesicle transportdefinition[GO:0048193]  
  • ISSOrtholog Curator
Inflammatory responsedefinition[GO:0006954]  
  • IEAUniProtKB KW
Innate immune responsedefinition[GO:0045087]  
  • IEAUniProtKB KW
Integrin-mediated signaling pathwaydefinition[GO:0007229]  
1
  • TASBHF-UCL
Intracellular signal transductiondefinition[GO:0035556]  
3
  • IGIBHF-UCL
Negative regulation of cell deathdefinition[GO:0060548]  
1
  • IMPUniProtKB
Negative regulation of endocytosisdefinition[GO:0045806]  
1
  • TASBHF-UCL
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDABHF-UCL
Positive regulation of angiogenesisdefinition[GO:0045766]  
3
  • IGIBHF-UCL
  • IMPUniProtKB
Positive regulation of blood vessel endothelial cell migrationdefinition[GO:0043536]  
2
  • IGIBHF-UCL
Positive regulation of CREB transcription factor activitydefinition[GO:0032793]  
1
  • IGIBHF-UCL
Positive regulation of endothelial cell chemotaxisdefinition[GO:2001028]  
1
  • IMPBHF-UCL
Positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0038033]  
2
  • IGIBHF-UCL
Positive regulation of endothelial cell migrationdefinition[GO:0010595]  
1
  • IMPUniProtKB
Positive regulation of endothelial cell proliferationdefinition[GO:0001938]  
1
  • IGIBHF-UCL
Positive regulation of histone deacetylase activitydefinition[GO:1901727]  
1
  • IGIBHF-UCL
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
1
  • IMPUniProtKB
Positive regulation of neuron projection developmentdefinition[GO:0010976]  
1
  • IMPUniProtKB
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
1
  • IMPUniProtKB
Positive regulation of osteoblast differentiationdefinition[GO:0045669]  
  • ISSOrtholog Curator
Positive regulation of peptidyl-serine phosphorylationdefinition[GO:0033138]  
1
  • IGIBHF-UCL
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • IMPBHF-UCL
Protein autophosphorylationdefinition[GO:0046777]  
1
  • TASBHF-UCL
Regulation of integrin-mediated signaling pathwaydefinition[GO:2001044]  
1
  • TASBHF-UCL
Regulation of keratinocyte proliferationdefinition[GO:0010837]  
  • ISSOrtholog Curator
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0048010]  
1
  • IMPBHF-UCL
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.13: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
  • CuratedUniProtKB
It is regulated in the following manner
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds DAG with high affinity and appears to play the dominant role in mediating translocation to the cell membrane and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol ester with higher affinity. Autophosphorylation of Ser-742 and phosphorylation of Ser-738 by PKC relieves auto-inhibition by the PH domain. Phosphorylation on Tyr-463 by the SRC-ABL1 pathway in response to oxidative stress, is also required for activation. Activated by DAPK1 under oxidative stress.  
3
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to Reactome, this protein belongs to the following pathway:
Sphingolipid de novo biosynthesis  REACT_115810  
 

Keywords

Biological process 
Angiogenesis  definition   [KW-0037]
Apoptosis  definition   [KW-0053]
Differentiation  definition   [KW-0221]
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Innate immunity  definition   [KW-0399]
Neurogenesis  definition   [KW-0524]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Protein_kinase_D1
GenomeRNAi: 5587
PRO: PR:Q15139
Chemistry
GuidetoPHARMACOLOGY: 1489