| URN | urn:agi-llid:5578 |
|---|---|
| Connectivity | 1136 |
| Name | Prkca |
| Description | protein kinase C, alpha |
| Notes | A294G mutation of protein kinase C alpha does not detectably affect its biochemical properties in vitro or in vivo, and is at least rare in thyroid neoplasias A294G mutation of protein kinase C alpha does not detectably affect its biochemical properties in vitro or in vivo, and is at least rare in thyroid neoplasias. Activation of PKCalpha stabilizes F-actin and thereby opposes the effect of PKCepsilon on membrane remodeling in T84 cells. Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha. Calcium-dependent involucrin expression is inversely regulated by protein kinase C (PKC)alpha and PKCdelta. Calpha activation and phosphorylation of syntaxin 4 and Munc18c are required for the cell surface expression of P-selectin and the consequent binding of neutrophils to endothelial cells. Cis activation of the basal promoter of the PKC alpha gene occurs through an activator protein-2-dependent, phorbol ester-responsive pathway, which suggests an autoregulatory manner of transcription in glioblastoma multiforme cells. Data show that protein kinase Calpha mediates the effect of antiarrhythmic peptide on gap junction conductance. Epidermal and hepatocyte growth factors, but not keratinocyte growth factor, modulate protein kinase Calpha translocation to the plasma membrane. Ets1 serves as an effector for PKCalpha to fulfil certain functions in cancer ce. Filamin A was identified as a direct binding partner of protein kinase Calpha; two binding sites were identified on filamin A; a Ca2+ and phospholipid-dependent association of the regulatory domain of protein kinase C with these sites was revealed. Four residues located near the calcium binding site of PKC alpha are critical for activation and in vivo membrane translocation of the enzyme. Il-2 increased protein kinase C alpha expression, but polysaccharide K decreased it. Inhibition of the oxidative burst, i.e., cellular desensitization, was clearly reversed in cells overexpressing PKC alpha, pointing to PKC alpha as the major transmitter in eliciting the oxidative burst in monocytes/macrophages. Isoforms of protein kinase C and their distribution in human adrenal cortex and tumors. Loss of protein kinase Calpha expression may enhance the tumorigenic potential of Gli1 in basal cell carcinoma. NAG-1 expression is up-regulated by TPA in LNCaP cells through a PKC-dependent pathway involving the activation of NF-kappa B. Only PKC-alpha is involved in the signal transduction cascade leading to neutrophil transepithelial migration. Our findings present original data that PKCalpha is the isoform specifically involved in the proliferation of primary human osteoblasts. PKC alpha expressed in human neutrophils can phosphorylate p47phox and induce both its translocation and NADPH oxidase activation as well as the binding of p47phox to the cytosolic fragment of p22phox. PKC alpha functions as a negative modulator of calcineurin-regulated retinoid X receptor responsive element-dependent transcription during T cell activation. PKC alpha is a critical regulatory element that is required for efficient regulatory volume decrease in HeLa cells. PKC alpha phosphorylates diacylglycerol kinase zeta in cells, and this phosphorylation inhibits its kinase activity to remove cellular diacylglycerol, thereby affecting cell growth. PKC alpha plays a necessary role in mediating calcium-induced differentiation. Failure to regulate PKC alpha in SCC4 carcinoma cells may underlie at least part of the failure of calcium to promote differentiation in these cells. PKC stimulation upregulates neuron-specific ELAV (nELAV) proteins (HuB, HuC, and HuD), and induces nELAV proteins to colocalize with the translocated PKCalpha isozyme on the cytoskeleton, with a concomitant increase of nELAV threonine phosphorylation. PKC-alpha and PKC-epsilon act cooperatively in regulating JNK activation in response to PMA. PKC-alpha-mediated NG2 phosphorylation at Thr(2256) is a key step for initiating cell polarization and motility. PKCA acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T-lymphocytes. PKCA has a major role in cytoskeleton-dependent avidity modulation of ALCAM. PKCalpha C1A-C2 interdomain interactions have a role in lipid-mediated PKCalpha activation. PKCalpha and betaII have roles in the regulation of membrane recycling. PKCalpha is involved in the regulation of Ca2+-induced platelet aggregation. PKCalpha is required for ET-1-induced human myometrial cell growth. PKCalpha is specifically required for TPA-induced ERK(MAPK) signaling to trigger gene expressions of p15(INK4b) and p16(INK4a) leading to HepG2 growth inhibition. PKCalpha may regulate Ets1 activity in invasive breast cancer cells. PKCalpha stimulates NO production in endothelial cells and plays a role in regulation of blood flow in vivo. PKCalpha-S100C/A11-mediated pathway is involved in and essential for the growth inhibition of normal human keratinocytes cells by TGFbeta1. PKD activation plays a central role in NT peptide secretion; upstream regulators of PKD include PKC-alpha and -delta and Rho/ROK. PRKCA-dependent PRKD1 activation modulates ERK signal pathway and endothelial cell proliferation by vascular endothelial growth factor A. 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. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. Protein kinase C alpha negatively regulates cell spreading and motility in breast cancer cells. Protein kinase C alpha plays an important role in activating store-operated Ca2+ channels (SOC) in human mesangial cells. Protein kinase C promotes apoptosis in LNCaP prostate cancer cells through activation of p38 MAPK and inhibition of the Akt survival pathway. REVIEW:Interaction of protein kinase C isozymes with membranes containing anionic phospholipids utilizing fluorescent phorbol esters to probe the properties of the C1 domains. Results demonstrate that a branched signaling pathway involving MEK, ERK, PKCepsilon, PKCalpha, and caveolin-1 regulates collagen expression in normal lung tissue and is perturbed during fibrosis. Results identify targets in RLIP76 for phosphorylation by protein kinase C alpha, which may act as substrates for differential transport of doxorubicin. Results propose a new mechanism by which lithium indirectly inhibits glycogen synthase kinase-3beta via phosphatidylinositol 3 kinase-dependent activation of protein kinase C alpha. Results suggest that the involvement of protein kinase C alpha in carbachol-induced soluble amyloid precursor protein (sAPPalpha) release is negligible, but PKC epsilon may be important in coupling cholinergic receptors with APP metabolism. The data do not support a strong association between single nucleotide polymorphism of PRKCA and spina bifida risk. The novel varepsilon and eta and atypical zeta, but not the conventional alpha and beta and the novel delta PKCs, may be involved in the signaling pathways involved in thrombin-induced human platelet P-selectin expression. There was expression of protein kinase C alpha in abnormal muscle fibers. Protein kinase C isoforms may play a role in the pathogenesis of myofibrillar myopathy. Use of PKC agonists and isozyme-specific pseudosubstrate peptide antagonists suggested a role for PKCalpha and -epsilon in VEGF-mediated DAF up-regulation, mediating A cytoprotective pathway in ECs. We analyzed the dependence of the expression of some selected protein kinase C isoenzymes on the availability and/or action of androgens. Activation required for vitamin C-succinate induced apoptosis of HL-60 cells. Autophosphorylation of PKCalpha limits its sensitivity to DAG; kinase inhibitors augment the DAG sensitivity of PKCalpha by destabilizing the closed conformation. Central role of PKC isoforms and the negative regulatory function of c-Src in the control of stromelysin 3 expression. Colocalizes with virus particles and is required for Respiratory syncytial virus (RSV) fusion to the cell membrane of bronchial epithelial cells. Data demonstrate a pathway of Rho activation involving protein kinase c alpha-dependent phosphorylation of p115Rho guanine exchange factor. Diacylglycerol-responsive PKC isoforms differentially influence CaR agonist-induced release of Ca2+ from internal stores. Greater increase of PKCalpha translocation after PMA treatment in breast cancer erythrocytes compared to controls was observed. In gastric cancer, protein translocation of PLCgamma2 and PKCalpha is critical event in the process of apoptosis induction. Phosphorylation of LRP by PKCalpha modulates the endocytic and signaling function of LRP by modifying its association with adaptor proteins. Protein kinase C alpha associates with phospholipase D1 and enhances basal phospholipase D activity in a protein phosphorylation-independent manner in melanoma cells, which contributes to the cell's high invasive potential. Protein kinase C alpha signaling is activated by apolipoprotein A-I, and it has a role in phosphorylation and stabilization of ATP binding cassette transporter A1 for the high density lipoprotein assembly. Protein kinase C alpha, iota, and theta binding to L-selectin cytoplasmic domain is modulated by receptor phosphorylation. Protein kinase C has a role in chitosan glutamate-mediated tight junction disruption. Protein kinase Calpha transcriptional repression via Sp1 by wild type p53 is involved in inhibition of multidrug resistance 1 P-glycoprotein phosphorylation. Protein phosphorylation and dephosphorylation via PKC and the corresponding protein phosphatases contribute to phosphatidylserine exposure and erythrocyte shrinkage after energy depletion. Role in induction of metallproteinases 1 and 3 in fibroblasts by basic calcium phosphate crystals. The affinity of isolated C1A and C1B domains of PKCalpha and PKCgamma for soluble and membrane-incorporated DAG and phorbol ester were measured by isothermal calorimetry and surface plasmon resonance in order to compare activation mechanisms. The direct PKC-dependent activation of the amyloid protein precursor secretory pathway is compromised by reduced PKCalpha expression and a specific role of this isoform in these mechanisms. The first report of focal adhesion kinase and phosphatidylinositol 3-kinase-dependent PKC-alpha activation in bacterial invasion related to cytoskeletal reorganization. There is a complex interplay between PKCalpha, Syk, and Src involving physical interaction, phosphorylation, translocation within the cell, and functional activity regulation. There is an impairment of degradation of protein kinase c alpha in huntington disease 150q cells that is connected with the sequestration of proteasome on mutant huntingtin aggregates. Two fatty acids inhibited the phorbol 12-myristate 13-acetate (PMA)-induced plasma membrane translocation of protein kinase C (PKC)-alpha and -epsilon. We used publicly available gene expression array data to further understand PKC-a-associated gene expression profiles in NSCLC. |
| Pathway | AdrenergicRb -> STAT3 signaling |
|---|---|
| vascular endothelial growth factor signaling pathway |
| GO Molecular Function | nucleotide binding |
|---|---|
| transferase activity | |
| ATP binding | |
| metal ion binding | |
| calcium ion binding | |
| zinc ion binding | |
| kinase activity | |
| protein kinase activity | |
| protein serine-threonine kinase activity | |
| protein kinase C activity | |
| histone kinase activity (H3-T6 specific) | |
| calcium-dependent protein kinase C activity |
| GO Cellular Component | protein complex |
|---|---|
| membrane | |
| plasma membrane | |
| cytoplasm | |
| membrane raft | |
| cytosol | |
| mitochondrion | |
| nucleus | |
| membrane fraction | |
| synaptosome |
| GO Biological Process | negative regulation of cell proliferation |
|---|---|
| aging | |
| establishment of protein localization | |
| positive regulation of synaptogenesis | |
| chondrocyte differentiation | |
| central nervous system neuron axonogenesis | |
| negative regulation of heart contraction | |
| regulation of muscle contraction | |
| regulation of the force of heart contraction | |
| learning or memory | |
| positive regulation of exocytosis | |
| inactivation of MAPK activity | |
| negative regulation of insulin receptor signaling pathway | |
| negative regulation of translation | |
| negative regulation of protein amino acid phosphorylation | |
| positive regulation of protein amino acid phosphorylation | |
| regulation of peptidyl-tyrosine phosphorylation | |
| negative regulation of protein kinase activity | |
| positive regulation of smooth muscle cell proliferation | |
| induction of apoptosis by extracellular signals | |
| induction of apoptosis by intracellular signals | |
| regulation of receptor-mediated endocytosis | |
| neutrophil chemotaxis | |
| protein amino acid phosphorylation | |
| peptidyl-threonine phosphorylation | |
| peptidyl-serine phosphorylation | |
| histone H3-T6 phosphorylation | |
| cellular calcium ion homeostasis | |
| response to mechanical stimulus | |
| response to antibiotic | |
| response to toxin | |
| response to reactive oxygen species | |
| response to organic cyclic substance | |
| response to ethanol | |
| response to interleukin-1 | |
| response to peptide hormone stimulus | |
| response to estradiol stimulus | |
| response to corticosterone stimulus | |
| induction of positive chemotaxis | |
| positive regulation of inflammatory response | |
| negative regulation of glucose import | |
| intracellular signaling pathway |
| Ariadne Ontology | PKC |
|---|
| Group | PKC |
|---|---|
| negative regulation of cell proliferation | |
| aging | |
| establishment of protein localization | |
| positive regulation of synaptogenesis | |
| chondrocyte differentiation | |
| central nervous system neuron axonogenesis | |
| negative regulation of heart contraction | |
| regulation of muscle contraction | |
| regulation of the force of heart contraction | |
| learning or memory | |
| positive regulation of exocytosis | |
| inactivation of MAPK activity | |
| negative regulation of insulin receptor signaling pathway | |
| negative regulation of translation | |
| negative regulation of protein amino acid phosphorylation | |
| positive regulation of protein amino acid phosphorylation | |
| regulation of peptidyl-tyrosine phosphorylation | |
| negative regulation of protein kinase activity | |
| positive regulation of smooth muscle cell proliferation | |
| induction of apoptosis by extracellular signals | |
| induction of apoptosis by intracellular signals | |
| regulation of receptor-mediated endocytosis | |
| neutrophil chemotaxis | |
| protein amino acid phosphorylation | |
| peptidyl-threonine phosphorylation | |
| peptidyl-serine phosphorylation | |
| histone H3-T6 phosphorylation | |
| cellular calcium ion homeostasis | |
| response to mechanical stimulus | |
| response to antibiotic | |
| response to toxin | |
| response to reactive oxygen species | |
| response to organic cyclic substance | |
| response to ethanol | |
| response to interleukin-1 | |
| response to peptide hormone stimulus | |
| response to estradiol stimulus | |
| response to corticosterone stimulus | |
| induction of positive chemotaxis | |
| positive regulation of inflammatory response | |
| negative regulation of glucose import | |
| intracellular signaling pathway | |
| nucleotide binding | |
| transferase activity | |
| ATP binding | |
| metal ion binding | |
| calcium ion binding | |
| zinc ion binding | |
| kinase activity | |
| protein kinase activity | |
| protein serine-threonine kinase activity | |
| protein kinase C activity | |
| histone kinase activity (H3-T6 specific) | |
| calcium-dependent protein kinase C activity | |
| protein complex | |
| membrane | |
| plasma membrane | |
| cytoplasm | |
| membrane raft | |
| cytosol | |
| mitochondrion | |
| nucleus | |
| membrane fraction | |
| synaptosome |
| MedScan ID | 5578 |
|---|
| Hugo ID | 9393 |
|---|
| Human chromosome position | 17q22-q23.2 |
|---|
| LocusLink ID | 5578 |
|---|---|
| 18750 | |
| 24680 | |
| 146784 | |
| 276901 | |
| 268497 |
| Alias | AAG6 |
|---|---|
| PKCA | |
| PRKACA | |
| MGC129900 | |
| MGC129901 | |
| PKC-alpha | |
| protein kinase C alpha type | |
| PKC-A | |
| aging-associated gene 6 | |
| AI875142 | |
| RP23-145G23.2 | |
| OTTMUSP00000003037 | |
| protein kinase c-alpha | |
| KPCA | |
| KPCA_HUMAN | |
| LOC146784 | |
| PRKCA | |
| protein kinase C alpha | |
| protein kinase C, alpha | |
| Protein kinase C, alpha type (PKC-alpha) (PKC-A) | |
| hypothetical protein LOC146784 |
| Organism | Homo sapiens |
|---|---|
| Mus musculus | |
| Rattus norvegicus |
| OMIM ID | 176960 |
|---|
| Mouse chromosome position | 11 68.0 cM |
|---|
| GO ID | 0005524 |
|---|---|
| 0004698 | |
| 0035403 | |
| 0046872 | |
| 0000166 | |
| 0004697 | |
| 0016740 | |
| 0008270 | |
| 0007568 | |
| 0006874 | |
| 0021955 | |
| 0002062 | |
| 0035408 | |
| 0000188 | |
| 0008624 | |
| 0008629 | |
| 0050930 | |
| 0023034 | |
| 0007611 | |
| 0008285 | |
| 0046325 | |
| 0045822 | |
| 0046627 | |
| 0001933 | |
| 0006469 | |
| 0017148 | |
| 0030593 | |
| 0018105 | |
| 0018107 | |
| 0045921 | |
| 0050729 | |
| 0001934 | |
| 0048661 | |
| 0051965 | |
| 0006937 | |
| 0050730 | |
| 0048259 | |
| 0002026 | |
| 0046677 | |
| 0051412 | |
| 0032355 | |
| 0045471 | |
| 0070555 | |
| 0009612 | |
| 0014070 | |
| 0043434 | |
| 0000302 | |
| 0009636 | |
| 0005737 | |
| 0005829 | |
| 0005624 | |
| 0045121 | |
| 0005739 | |
| 0005634 | |
| 0005886 | |
| 0043234 | |
| 0019717 | |
| 0016301 | |
| 0004672 | |
| 0004674 | |
| 0006468 | |
| 0016020 | |
| 0045184 | |
| 0005509 | |
| 0007242 | |
| 0019992 | |
| 0005515 | |
| 0007166 | |
| 0004682 | |
| 0004713 | |
| 0004691 | |
| 0000074 |
| Rat chromosome position | 10q32.1 |
|---|
| Swiss-Prot Accession | B5BU22 |
|---|---|
| P17252 | |
| Q7Z727 | |
| Q2TSD3 | |
| Q59FI5 | |
| P20444 | |
| Q4VA93 | |
| Q3TQ39 | |
| Q9R0Z6 | |
| P05696 | |
| Q15137 | |
| Q32M72 | |
| Q96RE4 |
| PIR ID | S09496 |
|---|---|
| S07104 |
| Unigene ID | Hs.531704 |
|---|---|
| Hs.708867 | |
| Mm.222178 | |
| Rn.207908 | |
| Hs.637776 | |
| Rn.86669 |
| KEGG ID | hsa:5578 |
|---|---|
| mmu:18750 | |
| rno:24680 |
| EC Number | 2.7.11.13 |
|---|---|
| 2.7.11.1 | |
| 2.7.1.37 |
| Swiss-Prot ID | KPCA_HUMAN |
|---|---|
| KPCA_MOUSE | |
| B5BU22_HUMAN | |
| Q4VA93_MOUSE | |
| Q7Z727_HUMAN |
| Cell Localization | Cytoplasm |
|---|---|
| Cell membrane |
| IPI ID | IPI00385449 |
|---|---|
| IPI00321446 | |
| IPI00884460 | |
| IPI00748556 | |
| IPI00652220 | |
| IPI00201792 | |
| IPI00781307 | |
| IPI00781159 | |
| IPI00780412 | |
| IPI00779055 | |
| IPI00766874 |
| Homologene ID | 55679 |
|---|
| RGD ID | 3395 |
|---|
| MGI ID | 97595 |
|---|