PKCA
a classical protein kinase C (PKC) downstream of many receptors. Classical PKCs are calcium-dependent enzymes that are activated by phosphatidylserine, diacylglycerol and phorbol esters. Contains a pseudo-substrate autoinhibitory domain that binds to the catalytic domain preventing its activation in the absence of cofactors or activators. Involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Associated with increases in cellular polarization and motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42. Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level, and the regulation of calcium-induced platelet aggregation. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Belongs to the AGC Ser/Thr protein kinase family, PKC subfamily. Note: This description may include information from UniProtKB.
Protein type: AGC group; EC 2.7.11.13; Kinase, protein; Oncoprotein; PKC family; PKCa subfamily; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor)
Molecular Function: ATP binding; calcium-dependent protein kinase C activity; enzyme binding; histone H3T6 kinase activity; integrin binding; lipid binding; protein binding; protein kinase activity; protein kinase C activity; protein serine kinase activity; protein serine/threonine kinase activity; zinc ion binding
Biological Process: angiogenesis; cell adhesion; cell population proliferation; cellular response to carbohydrate stimulus; central nervous system neuron axonogenesis; chondrocyte differentiation; chromatin remodeling; desmosome assembly; establishment of protein localization; induction of positive chemotaxis; intracellular calcium ion homeostasis; intracellular signal transduction; intrinsic apoptotic signaling pathway; learning or memory; muscle cell cellular homeostasis; negative regulation of anion channel activity; negative regulation of cell population proliferation; negative regulation of glial cell apoptotic process; negative regulation of glucose import; negative regulation of insulin receptor signaling pathway; negative regulation of MAPK cascade; negative regulation of protein kinase activity; negative regulation of protein phosphorylation; negative regulation of translation; neutrophil chemotaxis; peptidyl-serine autophosphorylation; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; positive regulation of angiogenesis; positive regulation of blood vessel endothelial cell migration; positive regulation of bone resorption; positive regulation of cardiac muscle hypertrophy; positive regulation of cell adhesion; positive regulation of cell migration; positive regulation of dense core granule biogenesis; positive regulation of endothelial cell migration; positive regulation of endothelial cell proliferation; positive regulation of ERK1 and ERK2 cascade; positive regulation of exocytosis; positive regulation of inflammatory response; positive regulation of lipopolysaccharide-mediated signaling pathway; positive regulation of macrophage differentiation; positive regulation of mitotic cell cycle; positive regulation of protein phosphorylation; positive regulation of smooth muscle cell proliferation; positive regulation of synapse assembly; post-translational protein modification; presynaptic modulation of chemical synaptic transmission; protein autophosphorylation; protein phosphorylation; regulation of muscle contraction; regulation of peptidyl-tyrosine phosphorylation; regulation of platelet aggregation; regulation of receptor-mediated endocytosis; regulation of response to osmotic stress; regulation of synaptic vesicle exocytosis; regulation of the force of heart contraction; response to corticosterone; response to estradiol; response to ethanol; response to interleukin-1; response to mechanical stimulus; response to organic cyclic compound; response to peptide hormone; response to reactive oxygen species; response to toxic substance; stem cell differentiation
