PRKCA - Protein kinase C alpha type - human protein (Function)
 
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PRKCA »  Protein kinase C alpha type   [ EC 2.7.11.13 ]  (PKC-A)
 
Gene name:  PRKCA
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
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  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Calcium-dependent protein kinase C activitydefinition[GO:0004698] silver  
  • IEAOrtholog Compara
Enzyme bindingdefinition[GO:0019899]  
1
  • IPIBHF-UCL
Histone kinase activity (H3-T6 specific)definition[GO:0035403]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
5
  • IPIIntAct
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • IDAUniProtKB
Protein kinase C activitydefinition[GO:0004697]  
  • ISSOrtholog Curator
Zinc ion bindingdefinition[GO:0008270] silver  
  • IEAInterPro 2 GO
GO biological process 
Activation of adenylate cyclase activitydefinition[GO:0007190]  
  • ISSOrtholog Curator
Angiogenesisdefinition[GO:0001525]  
  • IEAUniProtKB KW
Apoptotic signaling pathwaydefinition[GO:0097190]  
1
  • TASPINC
Cell adhesiondefinition[GO:0007155]  
  • IEAUniProtKB KW
Cellular calcium ion homeostasisdefinition[GO:0006874] silver  
  • IEAOrtholog Compara
Cellular response to carbohydrate stimulusdefinition[GO:0071322] silver  
  • IEAOrtholog Compara
Chondrocyte differentiationdefinition[GO:0002062] silver  
  • IEAOrtholog Compara
Desmosome assemblydefinition[GO:0002159]  
1
  • IMPBHF-UCL
Histone H3-T6 phosphorylationdefinition[GO:0035408]  
1
  • IDAUniProtKB
Inactivation of MAPK activitydefinition[GO:0000188] silver  
  • IEAOrtholog Compara
Induction of positive chemotaxisdefinition[GO:0050930] silver  
  • IEAOrtholog Compara
Intrinsic apoptotic signaling pathwaydefinition[GO:0097193] silver  
  • IEAOrtholog Compara
Negative regulation of adenylate cyclase activitydefinition[GO:0007194]  
  • ISSOrtholog Curator
Negative regulation of cell proliferationdefinition[GO:0008285] silver  
  • IEAOrtholog Compara
Negative regulation of glial cell apoptotic processdefinition[GO:0034351]  
1
  • IMPUniProtKB
Negative regulation of glucose importdefinition[GO:0046325] silver  
  • IEAOrtholog Compara
Negative regulation of insulin receptor signaling pathwaydefinition[GO:0046627] silver  
  • IEAOrtholog Compara
Neutrophil chemotaxisdefinition[GO:0030593] silver  
  • IEAOrtholog Compara
Peptidyl-serine autophosphorylationdefinition[GO:0036289] silver  
  • IEAOrtholog Compara
Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • IMPUniProtKB
Positive regulation of blood vessel endothelial cell migrationdefinition[GO:0043536]  
1
  • IDADFLAT
Positive regulation of cardiac muscle hypertrophydefinition[GO:0010613]  
  • ISSOrtholog Curator
Positive regulation of cell adhesiondefinition[GO:0045785]  
1
  • IMPUniProtKB
Positive regulation of dense core granule biogenesisdefinition[GO:2000707]  
  • ISSOrtholog Curator
Positive regulation of endothelial cell migrationdefinition[GO:0010595]  
1
  • IMPUniProtKB
Positive regulation of endothelial cell proliferationdefinition[GO:0001938]  
1
  • IMPUniProtKB
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
  • ISSOrtholog Curator
Positive regulation of inflammatory responsedefinition[GO:0050729] silver  
  • IEAOrtholog Compara
Positive regulation of lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031666]  
1
  • IMPUniProtKB
Positive regulation of macrophage differentiationdefinition[GO:0045651]  
  • ISSOrtholog Curator
Positive regulation of mitotic cell cycledefinition[GO:0045931]  
1
  • IMPUniProtKB
Positive regulation of protein phosphorylationdefinition[GO:0001934] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Regulation of muscle contractiondefinition[GO:0006937] silver  
  • IEAOrtholog Compara
Regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050730] silver  
  • IEAOrtholog Compara
Regulation of platelet aggregationdefinition[GO:0090330]  
1
  • IDAUniProtKB
Regulation of the force of heart contractiondefinition[GO:0002026] silver  
  • IEAOrtholog Compara
Response to interleukin-1definition[GO:0070555]  
1
  • IMPBHF-UCL
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.13: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Binds 3 calcium ions per subunit. The ions are bound to the C2 domain (By similarity).  
  • CuratedUniProtKB
It is regulated in the following manner
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.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
African trypanosomiasis  hsa05143+5578  
Aldosterone-regulated sodium reabsorption  hsa04960+5578  
Amoebiasis  hsa05146+5578  
Calcium signaling pathway  hsa04020+5578  
Cholinergic synapse  hsa04725+5578  
Dopaminergic synapse  hsa04728+5578  
Endocrine and other factor-regulated calcium reabsorption  hsa04961+5578  
ErbB signaling pathway  hsa04012+5578  
Fc epsilon RI signaling pathway  hsa04664+5578  
Fc gamma R-mediated phagocytosis  hsa04666+5578  
Focal adhesion  hsa04510+5578  
GABAergic synapse  hsa04727+5578  
Gap junction  hsa04540+5578  
Gastric acid secretion  hsa04971+5578  
Glioma  hsa05214+5578  
Glutamatergic synapse  hsa04724+5578  
GnRH signaling pathway  hsa04912+5578  
Influenza A  hsa05164+5578  
Leukocyte transendothelial migration  hsa04670+5578  
Long-term depression  hsa04730+5578  
Long-term potentiation  hsa04720+5578  
MAPK signaling pathway  hsa04010+5578  
Melanogenesis  hsa04916+5578  
Natural killer cell mediated cytotoxicity  hsa04650+5578  
Non-small cell lung cancer  hsa05223+5578  
Pancreatic secretion  hsa04972+5578  
Pathogenic Escherichia coli infection  hsa05130+5578  
Pathways in cancer  hsa05200+5578  
Phosphatidylinositol signaling system  hsa04070+5578  
Salivary secretion  hsa04970+5578  
Tight junction  hsa04530+5578  
Vascular smooth muscle contraction  hsa04270+5578  
VEGF signaling pathway  hsa04370+5578  
Vibrio cholerae infection  hsa05110+5578  
Wnt signaling pathway  hsa04310+5578  
According to Reactome, this protein belongs to the following pathways:
Disease  REACT_116125  
Extracellular matrix organization  REACT_118779  
Gene Expression  REACT_71  
Hemostasis  REACT_604  
Immune System  REACT_6900  
Metabolism  REACT_111217  
Metabolism of RNA  REACT_21257  
Neuronal System  REACT_13685  
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Angiogenesis  definition   [KW-0037]
Apoptosis  definition   [KW-0053]
Cell adhesion  definition   [KW-0130]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PKC_alpha
GenomeRNAi: 5578
PRO: PR:P17252
Chemistry
GuidetoPHARMACOLOGY: 1482