KinaseMD - PRKCD

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). View more >>

GO - Biological processes (BP): activation of protein kinase activity, apoptotic process, B cell proliferation, cell chemotaxis, cell cycle, 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, intracellular signal transduction, 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, negative regulation of protein binding, neutrophil activation, neutrophil degranulation, 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 signaling receptor activity, signal transduction, stimulatory C-type lectin receptor signaling pathway, termination of signal transduction View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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KinaseMD: Kinase mutations and drug responses

PRKCD

Entrez ID: 5580

Full name: protein kinase C delta

External links: HGNC UniprotKB Ensembl RefSeq COSMIC

Family: AGC: PKC: PKCd

Chromosomal location: 3p21.1

Substructure location: Gatekeeper: 427 A-loop: 490...513 G-loop: [N/A] αC-helix: [N/A]

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Kaplan plot for PRKCD in