PRKCD

Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein encoded by this gene is one of the PKC family members. Studies both in human and mice demonstrate that this kinase is involved in B cell signaling and in the regulation of growth, apoptosis, and differentiation of a variety of cell types. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq]

protein kinase C, delta

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 (PubMed:21810427, PubMed:21406692).
Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity).
Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21810427, PubMed:21406692).
In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21810427, PubMed:21406692).
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 (PubMed:21810427, PubMed:21406692).
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 (By similarity).
Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464).
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). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity).
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 (PubMed:19801500).
May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588).
In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418).
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 (PubMed:19587372).
Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440).
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).
Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167).
Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575).

Activation of protein kinase activityManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
B cell proliferationIEA:Ensembl
Cell chemotaxisManual Assertion Based On ExperimentIMP:UniProtKB
Cell cycleIEA:UniProtKB-KW
Cellular response to angiotensinManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to hydrogen peroxideManual Assertion Based On ExperimentIDA:ParkinsonsUK-UCL
Cellular response to hydroperoxideManual Assertion Based On ExperimentIDA:UniProtKB
Cellular response to UVManual Assertion Based On ExperimentIDA:UniProtKB
Cellular senescenceManual Assertion Based On ExperimentIMP:BHF-UCL
Defense response to bacteriumISS:UniProtKB
Fc-gamma receptor signaling pathway involved in phagocytosisTAS:Reactome
Histone phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Immunoglobulin mediated immune responseIEA:Ensembl
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Intrinsic apoptotic signaling pathway in response to oxidative stressManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Negative regulation of actin filament polymerizationISS:UniProtKB
Negative regulation of filopodium assemblyISS:UniProtKB
Negative regulation of glial cell apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of inflammatory response1 PublicationIC:BHF-UCL
Negative regulation of insulin receptor signaling pathwayISS:BHF-UCL
Negative regulation of MAP kinase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of peptidyl-tyrosine phosphorylationBy SimilarityISS:BHF-UCL
Negative regulation of platelet aggregationISS:UniProtKB
Negative regulation of protein bindingManual Assertion Based On ExperimentTAS:BHF-UCL
Neutrophil activationManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-threonine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of apoptotic signaling pathwayIEA:Ensembl
Positive regulation of ceramide biosynthetic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of endodeoxyribonuclease activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of glucosylceramide catabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of phospholipid scramblase activityManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of protein dephosphorylationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of protein import into nucleusManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of response to DNA damage stimulusManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of sphingomyelin catabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of superoxide anion generationManual Assertion Based On ExperimentIMP:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Protein stabilization1 PublicationNAS:UniProtKB
Regulation of actin cytoskeleton organizationManual Assertion Based On ExperimentIMP:CACAO
Regulation of ceramide biosynthetic processManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of mRNA stabilityTAS:Reactome
Regulation of signaling receptor activityManual Assertion Based On ExperimentTAS:BHF-UCL
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Termination of signal transductionManual Assertion Based On ExperimentIMP:BHF-UCL

Cytoplasm
Cytoplasm, perinuclear region
Nucleus
Cell membrane
Mitochondrion
Endomembrane system
Translocates to the mitochondria upon apoptotic stimulation. Upon activation, translocates to the plasma membrane followed by partial location to the endolysosomes (PubMed:17303575).

Autoimmune lymphoproliferative syndrome 3 (ALPS3):
A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. CVID9 patients have B-cell deficiency and severe autoimmunity.

Autophosphorylated and/or phosphorylated at Thr-507, within the activation loop; phosphorylation at Thr-507 is not a prerequisite for enzymatic activity (PubMed:19801500).
Autophosphorylated at Ser-299, Ser-302 and Ser-304 (PubMed:17603046).
Upon TNFSF10/TRAIL treatment, phosphorylated at Tyr-155; phosphorylation is required for its translocation to the endoplasmic reticulum and cleavage by caspase-3 (PubMed:15774464).
Phosphorylated at Tyr-313, Tyr-334 and Tyr-567; phosphorylation of Tyr-313 and Tyr-567 following thrombin or zymosan stimulation potentiates its kinase activity (PubMed:17570831).
Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2 (PubMed:11781095).
Phosphorylated at Tyr-313 through a SYK and SRC mechanism downstream of C-type lectin receptors activation, promoting its activation (By similarity).
Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation.