PRKCH
Description
The PRKCH (protein kinase C eta) is a protein-coding gene located on chromosome 14.
Protein kinase C eta type is an enzyme that in humans is encoded by the PRKCH gene. Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the 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. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription activation of the transglutaminase 1 (TGM1) gene.
PRKCH is a calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes, including cell differentiation in keratinocytes and pre-B cells, regulation of epithelial tight junction integrity, foam cell formation, and glioblastoma proliferation and apoptosis prevention. In keratinocytes, PRKCH binds and activates the tyrosine kinase FYN, which blocks epidermal growth factor receptor (EGFR) signaling, leading to growth arrest and differentiation. PRKCH also associates with the cyclin CCNE1-CDK2-CDKN1B complex, inhibiting CDK2 kinase activity and inducing G1 arrest. In association with RALA, PRKCH activates actin depolymerization, another crucial factor in keratinocyte differentiation. In pre-B cell receptor signaling, PRKCH functions downstream of BLNK, upregulating IRF4 and activating L chain gene rearrangement. PRKCH regulates epithelial tight junctions by phosphorylating occludin (OCLN), essential for their assembly and maintenance. In association with PLD2 and via TLR4 signaling, PRKCH participates in lipopolysaccharide (LPS)-induced RGS2 downregulation and foam cell formation. Upon PMA stimulation, PRKCH mediates glioblastoma cell proliferation by activating the mTOR pathway, PI3K/AKT pathway, and ERK1-dependent phosphorylation of ELK1. PRKCH protects glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, PRKCH regulates NF-kappa-B upstream signaling by activating IKBKB, protecting against DNA damage-induced apoptosis. PRKCH promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. PRKCH phosphorylates ATF2, promoting its nuclear retention, transcriptional activity, and negatively regulating its mitochondrial localization. PRKCH interacts with FYN, RALA, DGKQ, and PRKCH upstream open reading frame 2, which inhibits its kinase activity.
PRKCH is also known as PKC-L, PKCL, PRKCL, nPKC-eta, uORF2.
