LMP012456 UniProt Annotations
Gene Name protein kinase C, beta Protein Entry KPCB_RAT UniProt ID P68403 Species Rat
Comment type Description Alternative Products Event=Alternative splicing; Named isoforms=2; Name=Beta-I; IsoId=P68403-1, P04410-1; Sequence=Displayed; Name=Beta-II; IsoId=P68403-2, P04410-2; Sequence=VSP_004739; Catalytic Activity ATP + a protein = ADP + a phosphoprotein. Cofactor Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.; Enzyme Regulation Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615) (By similarity) 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. 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 (ANDR)-dependent transcription, by being recruited to ANDR 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. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1- MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. 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. {ECO:0000250, ECO:0000269|PubMed:10938109, ECO:0000269|PubMed:11714718, ECO:0000269|PubMed:19176525}. Interaction P18052:Ptpra (xeno); NbExp=3; IntAct=EBI-397072, EBI-6597520; Q8WV44-2:TRIM41 (xeno); NbExp=3; IntAct=EBI-397092, EBI-726015; Ptm Phosphorylation on Thr-500 of isoform beta-I, 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. Similarly, isoform beta-II is autophosphorylated on 'Thr-641' and 'Ser-660', subsequent to phosphorylation on Thr-500. Autophosphorylated 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. {ECO:0000269|PubMed:21215369, ECO:0000269|PubMed:7961692, ECO:0000269|PubMed:8327493, ECO:0000269|PubMed:8749392}. Similarity Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily Similarity Contains 1 AGC-kinase C-terminal domain Similarity Contains 1 C2 domain. {ECO:0000255|PROSITE- ProRule:PRU00041}. Similarity Contains 1 protein kinase domain Similarity Contains 2 phorbol-ester/DAG-type zinc fingers Subcellular Location Cytoplasm. Nucleus . Membrane; Peripheral membrane protein. Subunit Interacts with PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR (By similarity)
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