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  3. PRKCD

PRKCD (Protein kinase C delta)

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The Function of PRKCD

Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462).

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Protein names

Recommended name:

Protein kinase C delta type

Short name:

SDK1

Alternative name(s):

Tyrosine-protein kinase PRKCD
nPKC-delta
Sphingosine-dependent protein kinase-1

Top Gene-Substance Interactions

PRKCD Interacts with These Diseases

Disease Score

Substances That Increase PRKCD

Substances Interaction Organism Category

Substances That Decrease PRKCD

Substances Interaction Organism Category

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • NF-kappaB
  • CREB
  • AP-1
  • c-Jun
  • deltaCREB
  • STAT3
  • NF-kappaB1
  • c-Fos

Gene Pathways:

  • Disease
  • Immune System
  • Signal Transduction
  • Gene Expression
  • Hemostasis
  • Apoptosis
  • Tight junction
  • Chemokine signaling pathway
  • Neurotrophin signaling pathway
  • Vascular smooth muscle contraction
  • Metabolism of RNA
  • GnRH signaling pathway
  • Fc epsilon RI signaling pathway
  • Type II diabetes mellitus

Enzyme Regulation:

Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-507 (activation loop of the kinase domain), Ser-645 (turn motif) and Ser-664 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine.

Molecular Function:

  • Atp Binding
  • Calcium-Independent Protein Kinase C Activity
  • Enzyme Activator Activity
  • Enzyme Binding
  • Insulin Receptor Substrate Binding
  • Kinase Binding
  • Metal Ion Binding
  • Non-Membrane Spanning Protein Tyrosine Kinase Activity
  • Protein Kinase Binding
  • Protein Kinase C Activity
  • Protein Serine/Threonine Kinase Activity

Biological Processes:

  • Activation Of Phospholipase C Activity
  • Activation Of Protein Kinase Activity
  • Apoptotic Process
  • B Cell Proliferation
  • Cell Chemotaxis
  • Cell Cycle
  • Cellular Component Disassembly Involved In Execution Phase Of Apoptosis
  • Cellular Response To Angiotensin
  • Cellular Response To Hydrogen Peroxide
  • Cellular Response To Hydroperoxide
  • Cellular Senescence
  • Defense Response To Bacterium
  • Fc-Gamma Receptor Signaling Pathway Involved In Phagocytosis
  • Histone Phosphorylation
  • Immunoglobulin Mediated Immune Response
  • Interferon-Gamma-Mediated Signaling Pathway
  • Interleukin-10 Production
  • Interleukin-12 Production
  • Intrinsic Apoptotic Signaling Pathway In Response To Oxidative Stress
  • Negative Regulation Of Actin Filament Polymerization
  • Negative Regulation Of Filopodium Assembly
  • Negative Regulation Of Glial Cell Apoptotic Process
  • Negative Regulation Of Inflammatory Response
  • Negative Regulation Of Insulin Receptor Signaling Pathway
  • Negative Regulation Of Map Kinase Activity
  • Negative Regulation Of Peptidyl-Tyrosine Phosphorylation
  • Negative Regulation Of Platelet Aggregation
  • Neutrophil Activation
  • Peptidyl-Serine Phosphorylation
  • Peptidyl-Threonine Phosphorylation
  • Platelet Activation
  • Positive Regulation Of Apoptotic Signaling Pathway
  • Positive Regulation Of Ceramide Biosynthetic Process
  • Positive Regulation Of Endodeoxyribonuclease Activity
  • Positive Regulation Of Glucosylceramide Catabolic Process
  • Positive Regulation Of Phospholipid Scramblase Activity
  • Positive Regulation Of Protein Dephosphorylation
  • Positive Regulation Of Protein Import Into Nucleus
  • Positive Regulation Of Response To Dna Damage Stimulus
  • Positive Regulation Of Sphingomyelin Catabolic Process
  • Positive Regulation Of Superoxide Anion Generation
  • Protein Phosphorylation
  • Protein Stabilization
  • Regulation Of Actin Cytoskeleton Organization
  • Regulation Of Mrna Stability
  • Regulation Of Receptor Activity
  • Signal Transduction
  • Stimulatory C-Type Lectin Receptor Signaling Pathway
  • Termination Of Signal Transduction

Drug Bank:

  • Ingenol Mebutate
  • Tamoxifen
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| A306_12297| ALPS3| Anapl_05028| CB1_001347002| CVID9| D14Ertd420e| D623_10011907| H920_13386| I79_001470| M91_14522| MAY1| MDA_GLEAN10016595| N300_09980| N301_15078| N302_10094| N303_08643| N305_08629| N306_01593| N307_07818| N308_01311| N309_02487| N310_13642| N312_08777| N321_12666| N326_05951| N327_08000| N328_03061| N329_00485| N330_11372| N332_04785| N333_01355| N334_14010| N335_01426| N336_12889| N340_11228| N341_03236| nPKC-delta| PAL_GLEAN10022208| PANDA_007560| Pkcd| PKC[d]| PKCd1| PKCd2| PKCdelta| PKC-delta| PKCdelta1| PKCdelta2| prkcd-a| prkcd-b| protein kinase C[d]| protein kinase C, delta| protein kinase C, delta IV| protein kinase C delta type| protein kinase C delta type-like protein| protein kinase C, delta V| protein kinase C delta variant IX| protein kinase C delta VIII| tpa-1| TREES_T100010295| tyrosine-protein kinase PRKCD| UY3_03027| Y1Q_031940| Y956_07467| Z169_04601| prkcd

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