PRKCE

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.

Protein Kinase C Epsilon

Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546).

Apoptotic processManual Assertion Based On ExperimentTAS:ProtInc
Cell cycleIEA:UniProtKB-KW
Cell divisionIEA:UniProtKB-KW
Cell-substrate adhesionIEA:Ensembl
Cellular response to ethanolIEA:Ensembl
Cellular response to hypoxiaIEA:Ensembl
Cellular response to prostaglandin E stimulusIEA:Ensembl
Establishment of localization in cellIEA:Ensembl
Fc-gamma receptor signaling pathway involved in phagocytosisTAS:Reactome
Insulin secretionIEA:Ensembl
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Lipopolysaccharide-mediated signaling pathwayISS:UniProtKB
Locomotory exploration behaviorIEA:Ensembl
Macrophage activation involved in immune responseIEA:Ensembl
MAPK cascadeIEA:Ensembl
Mucus secretionIEA:Ensembl
Negative regulation of protein ubiquitinationIEA:Ensembl
Negative regulation of sodium ion transmembrane transporter activityManual Assertion Based On ExperimentTAS:BHF-UCL
Peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of actin filament polymerizationISS:UniProtKB
Positive regulation of cell-substrate adhesionIEA:Ensembl
Positive regulation of cellular glucuronidationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of cytokinesisManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of epithelial cell migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of fibroblast migrationISS:UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingIEA:Ensembl
Positive regulation of insulin secretionIEA:Ensembl
Positive regulation of lipid catabolic processIEA:Ensembl
Positive regulation of MAPK cascadeIEA:Ensembl
Positive regulation of mucus secretionIEA:Ensembl
Positive regulation of protein localization to plasma membraneManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Positive regulation of synaptic transmission, GABAergicIEA:Ensembl
Positive regulation of wound healingManual Assertion Based On ExperimentIMP:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of insulin secretion involved in cellular response to glucose stimulusIEA:Ensembl
Regulation of peptidyl-tyrosine phosphorylationIEA:Ensembl
Regulation of release of sequestered calcium ion into cytosolIEA:Ensembl
Response to morphineIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Synaptic transmission, GABAergicIEA:Ensembl
TRAM-dependent toll-like receptor 4 signaling pathwayISS:UniProtKB

Cytoplasm
Cytoplasm, cytoskeleton
Cell membrane
Cytoplasm, perinuclear region
Nucleus
Translocated to plasma membrane in epithelial cells stimulated by HGF (PubMed:17603037).
Associated with the Golgi at the perinuclear site in pre-passage fibroblasts (By similarity).
In passaging cells, translocated to the cell periphery (By similarity).
Translocated to the nucleus in PMA-treated cells (By similarity).

Phosphorylation on Thr-566 by PDPK1 triggers autophosphorylation on Ser-729. Phosphorylation in the hinge domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required for interaction with YWHAB.