The Function of PRKCB
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.
Protein names
Recommended name:
Protein kinase C beta typeShort name:
PKC-BAlternative name(s):
PKC-beta- RS198160 (PRKCB) ??
- RS7404095 (PRKCB) ??
- RS7404928 (PRKCB) ??
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Top Gene-Substance Interactions
PRKCB Interacts with These Diseases
Disease | Score |
Substances That Increase PRKCB
Substances | Interaction | Organism | Category |
Substances That Decrease PRKCB
Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Gene Pathways:
- Glutamatergic synapse
- Immune System
- Non-small cell lung cancer
- Neuronal System
- Hemostasis
- Melanogenesis
- Pathways in cancer
- Leishmaniasis
- Pancreatic secretion
- Vascular smooth muscle contraction
- Chemokine signaling pathway
- Leukocyte transendothelial migration
- Endocrine and other factor-regulated calcium reabsorption
- Calcium signaling pathway
- Phosphatidylinositol signaling system
- Salivary secretion
- Gastric acid secretion
- Long-term potentiation
- Aldosterone-regulated sodium reabsorption
- VEGF signaling pathway
- Fc epsilon RI signaling pathway
- Wnt signaling pathway
- Amoebiasis
- Carbohydrate digestion and absorption
- Glioma
- Long-term depression
- MAPK signaling pathway
- Signal Transduction
- Tight junction
- B cell receptor signaling pathway
- Natural killer cell mediated cytotoxicity
- African trypanosomiasis
- GnRH signaling pathway
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).
Cofactor:
Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.
Molecular Function:
- Androgen Receptor Binding
- Atp Binding
- Calcium Channel Regulator Activity
- Calcium-Dependent Protein Kinase C Activity
- Chromatin Binding
- Histone Binding
- Histone Kinase Activity (H3-T6 Specific)
- Ligand-Dependent Nuclear Receptor Transcription Coactivator Activity
- Protein Kinase C Activity
- Protein Kinase C Binding
- Protein Serine/Threonine Kinase Activity
- Zinc Ion Binding
Biological Processes:
- Adaptive Immune Response
- Apoptotic Process
- B Cell Activation
- B Cell Receptor Signaling Pathway
- Calcium Ion Transport
- Cellular Calcium Ion Homeostasis
- Cellular Response To Carbohydrate Stimulus
- Histone H3-T6 Phosphorylation
- Intracellular Signal Transduction
- Lipoprotein Transport
- Mitotic Nuclear Envelope Disassembly
- Negative Regulation Of Glucose Transport
- Negative Regulation Of Insulin Receptor Signaling Pathway
- Peptidyl-Serine Phosphorylation
- Platelet Activation
- Positive Regulation Of Angiogenesis
- Positive Regulation Of B Cell Receptor Signaling Pathway
- Positive Regulation Of I-Kappab Kinase/Nf-Kappab Signaling
- Positive Regulation Of Nf-Kappab Transcription Factor Activity
- Positive Regulation Of Vascular Endothelial Growth Factor Receptor Signaling Pathway
- Protein Phosphorylation
- Regulation Of Transcription From Rna Polymerase Ii Promoter
- Response To Hypoxia
- Signal Transduction
- Transcription, Dna-Templated