PRKCB

Description

The PRKCB (protein kinase C beta) is a protein-coding gene located on chromosome 16.

PRKCB (Protein Kinase C Beta) is a calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in numerous cellular processes including regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling, and endothelial cell proliferation. It plays a crucial role in B-cell activation by regulating BCR-induced NF-kappa-B activation. PRKCB directly phosphorylates CARD11/CARMA1 at Ser-559, Ser-644, and Ser-652, activating the canonical NF-kappa-B pathway (NFKB1). This phosphorylation leads to CARD11/CARMA1 association with lipid rafts and the recruitment of the BCL10-MALT1 complex and MAP3K7/TAK1, ultimately activating the IKK complex, resulting in nuclear translocation and activation of NFKB1. Additionally, PRKCB directly regulates BCR signaling through negative feedback by phosphorylating BTK at Ser-180, modulating its localization and inhibiting its activity. PRKCB is involved in oxidative stress-induced apoptosis by phosphorylating Ser-36 of p66Shc, promoting its mitochondrial accumulation and reactive oxygen species production. It functions as a coactivator of androgen receptor (AR)-dependent transcription by being recruited to AR target genes and phosphorylating Thr-6 of histone H3 (H3T6ph), an epigenetic marker for transcriptional activation that prevents H3K4me demethylation by LSD1/KDM1A. In insulin signaling, PRKCB may function downstream of IRS1 in muscle cells, mediating insulin-dependent DNA synthesis via the RAF1-MAPK/ERK signaling cascade. It also participates in regulating glucose transport in adipocytes by modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4 and promoting glucose uptake by phosphorylating SLC2A1/GLUT1. In pancreatic beta-cells, PRKCB may inhibit insulin gene transcription under high glucose by regulating MYC expression. In endothelial cells, PRKCB activation promotes phosphorylation of RB1, enhances VEGFA-induced cell proliferation, and inhibits insulin-dependent NOS3/eNOS regulation via PI3K/AKT, contributing to endothelial dysfunction. Additionally, PRKCB is involved in triglyceride homeostasis and phosphorylates ATF2, promoting its cooperation with JUN and transcriptional activation. It also phosphorylates KLHL3 in response to angiotensin II signaling, decreasing its interaction with WNK4. PRKCB interacts with PDK1, PRKCBP1, PHLPP1, PHLPP2, KDM1A/LSD1, PKN1, and AR.

PRKCB is also known as PKC-beta, PKCB, PKCI(2), PKCbeta, PRKCB1, PRKCB2.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing