PRKCB
Protein kinase C (PKC) is a family of serine-and threonine-specific protein kinases that can be activated by calcium and 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 a distinct role in cells.
Function
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity (PubMed:11598012).
Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (AR)-dependent transcription, by being recruited to AR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A (PubMed:20228790).
In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1 (PubMed:25982116).
Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity).
Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription (PubMed:19176525).
Biological Process
Adaptive immune responseIEA:UniProtKB-KW
Apoptotic processIEA:UniProtKB-KW
B cell activationISS:UniProtKB
B cell receptor signaling pathwayISS:UniProtKB
Calcium ion transportIEA:Ensembl
Cellular calcium ion homeostasisIEA:Ensembl
Cellular response to carbohydrate stimulusIEA:Ensembl
Chromatin organizationIEA:UniProtKB-KW
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Lipoprotein transportManual Assertion Based On ExperimentTAS:BHF-UCL
Mitotic nuclear membrane disassemblyTAS:Reactome
Negative regulation of glucose transmembrane transportISS:UniProtKB
Negative regulation of insulin receptor signaling pathwayISS:UniProtKB
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of angiogenesisISS:UniProtKB
Positive regulation of B cell receptor signaling pathwayISS:UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingISS:UniProtKB
Positive regulation of NF-kappaB transcription factor activityISS:UniProtKB
Positive regulation of vascular endothelial growth factor receptor signaling pathwayISS:UniProtKB
Post-translational protein modificationManual Assertion Based On ExperimentIDA:UniProtKB
Presynaptic modulation of chemical synaptic transmissionIEA:Ensembl
Protein phosphorylationManual Assertion Based On ExperimentTAS:ProtInc
Regulation of glucose transmembrane transportManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of synaptic vesicle exocytosisIEA:Ensembl
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:UniProtKB
Signal transduction1 PublicationNAS:ProtInc
PTM
Phosphorylation on Thr-500 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Autophosphorylation on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade (By similarity).