The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Prkca  -  protein kinase C, alpha

Rattus norvegicus

Synonyms: PKC-A, PKC-alpha, Pkca, Protein kinase C alpha type
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Prkca


High impact information on Prkca

  • Here we identify PKC-alpha as a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes [6].
  • Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by sensing intracellular Ca(2+) and signal transduction events, which can profoundly affect propensity toward heart failure [6].
  • Adenoviral gene transfer of dominant-negative or wild-type PKC-alpha into cardiac myocytes enhances or reduces contractility, respectively [6].
  • Here, we report that overexpression of the reported mutant PKC alpha complementary DNA in three fibroblast cell lines, including BALB/c 3T3, does not enable these cells to grow in soft agar or nude mice [7].
  • These results fail to confirm the previous study and indicate that overexpression of either the wild-type or the reported mutant form of PKC alpha does not transform rodent fibroblasts [7].

Chemical compound and disease context of Prkca


Biological context of Prkca


Anatomical context of Prkca

  • PKC-alpha was found only in beta-cells, PKC-gamma in alpha-cells, and PKC-epsilon in delta-cells and vascular walls [18].
  • PC-PLD activation was also accompanied by increases in total DAG production and increases in the translocation of both PKC enzyme activity and DAG-sensitive PKC-alpha, -beta, -delta, and -epsilon from the cytosol to the membrane fraction [19].
  • Effects of phorbol esters on PKC-alpha redistribution to the plasma membrane, however, were much greater than those of insulin [20].
  • Immunoreactivity of PKC-alpha, -beta, and -epsilon also indicated that their levels are diminished in fa/fa soleus muscle by 70-90% [21].
  • At least three different phorbol ester-sensitive PKC isoenzymes are expressed in neonatal rat ventricular myocytes (NRVMs): PKC-alpha, -delta, and -epsilon [3].

Associations of Prkca with chemical compounds

  • PKC alpha was found to separate into two peaks on hydroxylapatite chromatography [22].
  • Furthermore, it is shown that PKC alpha forms dimers via inter-molecular interactions between the C1 and C2 domains of two neighboring molecules [23].
  • Taken together, PKC-alpha is activated when cells are depolarized by a high concentration of potassium or glucose [2].
  • ET-1 and PHE, to much lesser extent, produced a rapid (0-5 min) translocation of PKC- immunoreactivity from the cytosol to the membrane fraction, whereas no intracellular redistribution of PKC-alpha, -delta and -xi immunoreactivities was observed [24].
  • PKC alpha overexpression in cardiomyocytes caused marked repression of triiodothyronine (T3)-responsive genes, alpha-myosin heavy chain, and the sarcoplasmic reticulum calcium-activated adenosinetriphosphatase SERCA2 [25].

Physical interactions of Prkca

  • The PKC-alpha binding domain of rPLD1 was localized to its N-terminus [26].
  • Furthermore, it was found that alpha C1A-C1B bound to a peptide containing the C2 domain of PKC alpha [23].
  • We speculated that the reason for changes after TPA treatment was the interactions with activated PKC alpha, which provoked syndecan-4/PKC alpha complex translocation to integrins [27].

Enzymatic interactions of Prkca


Regulatory relationships of Prkca

  • These results suggest that a covalent bridge between vicinal thiol groups of cell surface proteins induced by PAO potentiates PLD activation and that PAO-induced PLD activation is regulated by Ca2+ and PKC alpha and/or beta isozymes [29].
  • These results suggest that in the antigen-mediated PLD pathway PKC may be implicated but not play such a great role as PMA-stimulated pathway which is mediated through PKC alpha or beta [30].
  • PMA treatment or PKC-alpha overexpression also inhibited the tyrosine phosphorylation of IRS-1 [31].
  • Insulin inhibits secretin-induced ductal secretion by activation of PKC alpha and inhibition of PKA activity [32].
  • Insulin-like growth factor-1 also induced nuclear translocation of endogenous PKC-alpha [3].

Other interactions of Prkca

  • Peak I reacted exclusively with antisera to PKC gamma, peak II with PKC beta I and -beta II, and peak III with PKC alpha [33].
  • PKC alpha, -beta and -gamma isoenzymes separated by hydroxylapatite chromatography all cross-reacted with anti-PKC zeta [22].
  • Interestingly, PLD1 was associated with PKC-alpha or beta II, and its association gradually increased as NGF-induced neuronal differentiation progressed [34].
  • These results suggest that PKC alpha activity as well as p38MAPK activity is associated with TNF alpha induction in LPS-stimulated microglia [35].
  • Thus, in GH4C1 cells, Ca2(+)-independent nPKC epsilon may play a crucial role distinct from that mediated by Ca2(+)-dependent PKC alpha and beta II in a cellular response elicited by both TRH and phorbol esters [36].

Analytical, diagnostic and therapeutic context of Prkca


  1. Characterization of protein kinase C beta isoform activation on the gene expression of transforming growth factor-beta, extracellular matrix components, and prostanoids in the glomeruli of diabetic rats. Koya, D., Jirousek, M.R., Lin, Y.W., Ishii, H., Kuboki, K., King, G.L. J. Clin. Invest. (1997) [Pubmed]
  2. Bimodal role of conventional protein kinase C in insulin secretion from rat pancreatic beta cells. Zhang, H., Nagasawa, M., Yamada, S., Mogami, H., Suzuki, Y., Kojima, I. J. Physiol. (Lond.) (2004) [Pubmed]
  3. Protein kinase C-alpha-induced hypertrophy of neonatal rat ventricular myocytes. Vijayan, K., Szotek, E.L., Martin, J.L., Samarel, A.M. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  4. Changes in protein kinase C isozymes in the rat hippocampus following transient hypoxia. Yamaoka, Y., Shimohama, S., Kimura, J., Fukunaga, R., Taniguchi, T. Neurosci. Lett. (1993) [Pubmed]
  5. Alteration of protein kinase C isoforms in the liver of septic rat. Hsu, C., Hsieh, Y.C., Hsu, H.K., Jao, S.C., Yang, R.C. Shock (2002) [Pubmed]
  6. PKC-alpha regulates cardiac contractility and propensity toward heart failure. Braz, J.C., Gregory, K., Pathak, A., Zhao, W., Sahin, B., Klevitsky, R., Kimball, T.F., Lorenz, J.N., Nairn, A.C., Liggett, S.B., Bodi, I., Wang, S., Schwartz, A., Lakatta, E.G., DePaoli-Roach, A.A., Robbins, J., Hewett, T.E., Bibb, J.A., Westfall, M.V., Kranias, E.G., Molkentin, J.D. Nat. Med. (2004) [Pubmed]
  7. Failure of wild-type or a mutant form of protein kinase C-alpha to transform fibroblasts. Borner, C., Filipuzzi, I., Weinstein, I.B., Imber, R. Nature (1991) [Pubmed]
  8. Activation of protein kinase C alpha and delta by bile acids: correlation with bile acid structure and diacylglycerol formation. Rao, Y.P., Stravitz, R.T., Vlahcevic, Z.R., Gurley, E.C., Sando, J.J., Hylemon, P.B. J. Lipid Res. (1997) [Pubmed]
  9. Increased expression of liver PKC alpha in hypoinsulinemic diabetic rats: a post-translational effect. Nivet, V., Antoine, P.J., Amessou, M., Descamps, G., Desbuquois, B., Clot, J.P., Durand, D. Mol. Cell. Endocrinol. (1998) [Pubmed]
  10. Chloroquine induces the expression of inducible nitric oxide synthase in C6 glioma cells. Chen, T.H., Chang, P.C., Chang, M.C., Lin, Y.F., Lee, H.M. Pharmacol. Res. (2005) [Pubmed]
  11. Cloning and characterization of the murine PKC alpha promoter: identification of a retinoic acid response element. Desai, D.S., Hirai, S., Karnes, W.E., Niles, R.M., Ohno, S. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  12. A nuclease-resistant protein kinase C alpha ribozyme blocks glioma cell growth. Sioud, M., Sørensen, D.R. Nat. Biotechnol. (1998) [Pubmed]
  13. 1,25 dihydroxyvitamin D3 stimulates phospholipase C-gamma in rat colonocytes: role of c-Src in PLC-gamma activation. Khare, S., Bolt, M.J., Wali, R.K., Skarosi, S.F., Roy, H.K., Niedziela, S., Scaglione-Sewell, B., Aquino, B., Abraham, C., Sitrin, M.D., Brasitus, T.A., Bissonnette, M. J. Clin. Invest. (1997) [Pubmed]
  14. The regulatory domain of protein kinase C coordinates four atoms of zinc. Quest, A.F., Bloomenthal, J., Bardes, E.S., Bell, R.M. J. Biol. Chem. (1992) [Pubmed]
  15. Kinetic analysis of protein kinase C inhibition by staurosporine: evidence that inhibition entails inhibitor binding at a conserved region of the catalytic domain but not competition with substrates. Ward, N.E., O'Brian, C.A. Mol. Pharmacol. (1992) [Pubmed]
  16. PKC alpha mediates maternal touch regulation of growth-related gene expression in infant rats. Schanberg, S.M., Ingledue, V.F., Lee, J.Y., Hannun, Y.A., Bartolome, J.V. Neuropsychopharmacology (2003) [Pubmed]
  17. A role for protein kinase C-epsilon in angiotensin II stimulation of phospholipase D in rat renal mesangial cells. Pfeilschifter, J., Huwiler, A. FEBS Lett. (1993) [Pubmed]
  18. Age-dependent expression of protein kinase C isoforms in rat islets. Fletcher, D.J., Ways, D.K. Diabetes (1991) [Pubmed]
  19. Insulin stimulates phospholipase D-dependent phosphatidylcholine hydrolysis, Rho translocation, de novo phospholipid synthesis, and diacylglycerol/protein kinase C signaling in L6 myotubes. Standaert, M.L., Bandyopadhyay, G., Zhou, X., Galloway, L., Farese, R.V. Endocrinology (1996) [Pubmed]
  20. Effects of insulin and phorbol esters on subcellular distribution of protein kinase C isoforms in rat adipocytes. Farese, R.V., Standaert, M.L., Francois, A.J., Ways, K., Arnold, T.P., Hernandez, H., Cooper, D.R. Biochem. J. (1992) [Pubmed]
  21. Decreased expression of protein kinase-C alpha, beta, and epsilon in soleus muscle of Zucker obese (fa/fa) rats. Cooper, D.R., Watson, J.E., Dao, M.L. Endocrinology (1993) [Pubmed]
  22. Identification and characterization of protein kinase C zeta-immunoreactive proteins. Allen, B.G., Andrea, J.E., Walsh, M.P. J. Biol. Chem. (1994) [Pubmed]
  23. Regulation of PKC alpha activity by C1-C2 domain interactions. Slater, S.J., Seiz, J.L., Cook, A.C., Buzas, C.J., Malinowski, S.A., Kershner, J.L., Stagliano, B.A., Stubbs, C.D. J. Biol. Chem. (2002) [Pubmed]
  24. Cross-talk between receptor-mediated phospholipase C-beta and D via protein kinase C as intracellular signal possibly leading to hypertrophy in serum-free cultured cardiomyocytes. Eskildsen-Helmond, Y.E., Bezstarosti, K., Dekkers, D.H., van Heugten, H.A., Lamers, J.M. J. Mol. Cell. Cardiol. (1997) [Pubmed]
  25. Nuclear localization of protein kinase C-alpha induces thyroid hormone receptor-alpha1 expression in the cardiomyocyte. Kenessey, A., Sullivan, E.A., Ojamaa, K. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  26. Phospholipase D is associated in a phorbol ester-dependent manner with protein kinase C-alpha and with a 220-kDa protein which is phosphorylated on serine and threonine. Min, D.S., Exton, J.H. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  27. Syndecan-4 distribution during the differentiation of satellite cells isolated from soleus muscle treated by phorbol ester and calphostin C. Brzóska, E., Grabowska, I., Wróbel, E., Moraczewski, J. Cell. Mol. Biol. Lett. (2003) [Pubmed]
  28. Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. Sánchez-Pérez, A.M., Felipo, V. Neurochem. Int. (2005) [Pubmed]
  29. Phenylarsine oxide (PAO)-mediated activation of phospholipase D in rat basophilic leukemia (RBL-2H3) cells: possible involvement of calcium and protein kinase C. Kumada, T., Nakashima, S., Nakamura, Y., Miyata, H., Nozawa, Y. Immunobiology (1996) [Pubmed]
  30. Antigen-mediated phospholipase D activation in rat basophilic leukemia (RBL-2H3) cells: possible involvement of calcium/calmodulin. Kumada, T., Nakashima, S., Nakamura, Y., Miyata, H., Nozawa, Y. Biochim. Biophys. Acta (1995) [Pubmed]
  31. Lysophosphatidylcholine inhibits insulin-induced Akt activation through protein kinase C-alpha in vascular smooth muscle cells. Motley, E.D., Kabir, S.M., Gardner, C.D., Eguchi, K., Frank, G.D., Kuroki, T., Ohba, M., Yamakawa, T., Eguchi, S. Hypertension (2002) [Pubmed]
  32. Insulin inhibits secretin-induced ductal secretion by activation of PKC alpha and inhibition of PKA activity. Lesage, G.D., Marucci, L., Alvaro, D., Glaser, S.S., Benedetti, A., Marzioni, M., Patel, T., Francis, H., Phinizy, J.L., Alpini, G. Hepatology (2002) [Pubmed]
  33. Tissue and cellular distribution of the extended family of protein kinase C isoenzymes. Wetsel, W.C., Khan, W.A., Merchenthaler, I., Rivera, H., Halpern, A.E., Phung, H.M., Negro-Vilar, A., Hannun, Y.A. J. Cell Biol. (1992) [Pubmed]
  34. Expression and regulation of phospholipase D during neuronal differentiation of PC12 cells. Min, D.S., Ahn, B.H., Rhie, D.J., Yoon, S.H., Hahn, S.J., Kim, M.S., Jo, Y.H. Neuropharmacology (2001) [Pubmed]
  35. Protein kinase C alpha requirement in the activation of p38 mitogen-activated protein kinase, which is linked to the induction of tumor necrosis factor alpha in lipopolysaccharide-stimulated microglia. Nakajima, K., Tohyama, Y., Kohsaka, S., Kurihara, T. Neurochem. Int. (2004) [Pubmed]
  36. Possible role of Ca2(+)-independent protein kinase C isozyme, nPKC epsilon, in thyrotropin-releasing hormone-stimulated signal transduction: differential down-regulation of nPKC epsilon in GH4C1 cells. Akita, Y., Ohno, S., Yajima, Y., Suzuki, K. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  37. Microtubule-dependent PKC-alpha localization in A7r5 smooth muscle cells. Dykes, A.C., Fultz, M.E., Norton, M.L., Wright, G.L. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  38. Alterations in brain protein kinase C after experimental brain injury. Padmaperuma, B., Mark, R., Dhillon, H.S., Mattson, M.P., Prasad, M.R. Brain Res. (1996) [Pubmed]
  39. The occurrence of three isoenzymes of protein kinase C (alpha, beta and gamma) in retinas of different species. Osborne, N.N., Barnett, N.L., Morris, N.J., Huang, F.L. Brain Res. (1992) [Pubmed]
  40. Ca(2+)-dependent protein kinase C isoforms in rat pituitary hyperplasia: effect of in vivo treatment with quinagolide. Lévy, L., Alvaro, V., Dubray, C., Joubert, D. Eur. J. Pharmacol. (1994) [Pubmed]
WikiGenes - Universities