The Function of PRKCA
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. 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, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. 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. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), 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 mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. 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). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.
Protein names
Recommended name:
Protein kinase C alpha typeShort name:
PKC-AAlternative name(s):
PKC-alpha- RS10048158 (PRKCA) ??
- RS1005651 (PRKCA) ??
- RS11079657 (PRKCA) ??
- RS11651708 (PRKCA) ??
- RS11867410 (PRKCA) ??
- RS228883 (PRKCA) ??
- RS3889237 (PRKCA) ??
- RS4790904 (PRKCA) ??
- RS4791051 (PRKCA) ??
- RS7207499 (PRKCA) ??
- RS9892651 (PRKCA) ??
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Top Gene-Substance Interactions
PRKCA Interacts with These Diseases
Disease | Score |
Substances That Increase PRKCA
Substances | Interaction | Organism | Category |
Substances That Decrease PRKCA
Substances | Interaction | Organism | Category |
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Gene Pathways:
- Metabolism
- Disease
- Immune System
- MAPK signaling pathway
- Pathways in cancer
- Signal Transduction
- Gene Expression
- Melanogenesis
- Wnt signaling pathway
- Calcium signaling pathway
- Hemostasis
- Natural killer cell mediated cytotoxicity
- Leukocyte transendothelial migration
- Pathogenic Escherichia coli infection
- Tight junction
- Pancreatic secretion
- Vascular smooth muscle contraction
- Extracellular matrix organization
- Glioma
- Phosphatidylinositol signaling system
- African trypanosomiasis
- Aldosterone-regulated sodium reabsorption
- Amoebiasis
- Gastric acid secretion
- Glutamatergic synapse
- Long-term depression
- Metabolism of RNA
- Neuronal System
- VEGF signaling pathway
- Endocrine and other factor-regulated calcium reabsorption
- GnRH signaling pathway
- Salivary secretion
- Fc epsilon RI signaling pathway
- Long-term potentiation
- Non-small cell lung cancer
Enzyme Regulation:
Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-497 (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-657 (hydrophobic region), need to be phosphorylated for its full activation.
Cofactor:
Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.
Molecular Function:
- Atp Binding
- Calcium-Dependent Protein Kinase C Activity
- Enzyme Binding
- Histone Kinase Activity (H3-T6 Specific)
- Protein Kinase C Activity
- Protein Serine/Threonine Kinase Activity
- Zinc Ion Binding
Biological Processes:
- Activation Of Adenylate Cyclase Activity
- Angiogenesis
- Apoptotic Signaling Pathway
- Cell Adhesion
- Desmosome Assembly
- Histone H3-T6 Phosphorylation
- Intracellular Signal Transduction
- Mitotic Nuclear Envelope Disassembly
- Negative Regulation Of Adenylate Cyclase Activity
- Negative Regulation Of Glial Cell Apoptotic Process
- Peptidyl-Serine Phosphorylation
- Platelet Activation
- Positive Regulation Of Angiogenesis
- Positive Regulation Of Blood Vessel Endothelial Cell Migration
- 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 Lipopolysaccharide-Mediated Signaling Pathway
- Positive Regulation Of Macrophage Differentiation
- Positive Regulation Of Mitotic Cell Cycle
- Protein Phosphorylation
- Regulation Of Insulin Secretion
- Regulation Of Mrna Stability
- Regulation Of Platelet Aggregation
- Response To Interleukin-1