Function
Protein kinase C beta (PKCβ) is a calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in a wide array of 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 modulating BCR-induced NF-κB activation. PKCβ mediates the activation of the canonical NF-κB pathway (NFKB1) by directly phosphorylating CARD11/CARMA1 at Ser-559, Ser-644, and Ser-652. This phosphorylation triggers CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex, along with MAP3K7/TAK1, which subsequently activates the IKK complex, leading to nuclear translocation and activation of NFKB1. PKCβ directly participates in the negative feedback regulation of BCR signaling by down-modulating BTK function via direct phosphorylation of BTK at Ser-180. This phosphorylation alters BTK plasma membrane localization and inhibits BTK activity. PKCβ is implicated in apoptosis following oxidative damage. Under oxidative conditions, PKCβ specifically phosphorylates Ser-36 of the p66Shc isoform of SHC1, resulting in mitochondrial accumulation of p66Shc, where it functions as a reactive oxygen species producer. PKCβ 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). This phosphorylation is a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 Lys-4 (H3K4me) by LSD1/KDM1A. In insulin signaling, PKCβ may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. It participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. PKCβ phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1. Under high glucose conditions in pancreatic beta-cells, PKCβ is likely involved in the inhibition of 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, leading to endothelial dysfunction. PKCβ is also involved in triglyceride homeostasis. It phosphorylates ATF2, which promotes cooperation between ATF2 and JUN, activating transcription.