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Gene Review

PRKCA  -  protein kinase C, alpha

Bos taurus

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Disease relevance of PRKCA


High impact information on PRKCA

  • Monoclonal antibodies against the bovine PKC alpha plus beta or gamma isozymes immunostained dorsal and ventral ectoderm, respectively, which suggests different localizations of PKC isozymes [5].
  • In contrast, antisense PKC-alpha oligonucleotides enhanced VEGF-stimulated cell growth with a simultaneous decrease of 70% in PKC-alpha protein content [6].
  • We have expressed pools of bovine PKC alpha cDNAs mutagenized by Bal 31 deletion of internal, amino-terminal, or carboxyl-terminal sequences and have identified three classes of mutants on the basis of their distinct yeast phenotypes [7].
  • Treatment with 1,25-(OH)2-D3 (100 nM, 24 h) enhances plasma membrane association of PKC alpha and induces translocation of PKC beta to the nuclear membrane [8].
  • By site-directed mutagenesis of the PKC alpha cDNA, it has been shown that a region including 3 threonine residues (Thr-494, Thr-495, and Thr-497), present in the catalytic domain, is involved in controlling PKC activity [9].

Chemical compound and disease context of PRKCA


Biological context of PRKCA

  • Coexpression of this PKC alpha mutant and wild type PKC beta demonstrates that the mutant has a dominant effect upon PKC beta phosphorylation [9].
  • In contrast to rapid transient PKC translocation seen in response to agents which interact with membrane receptors to induce phospholipid hydrolysis, modulation of PKC alpha and PKC beta is observed after 24 h treatment with 1,25-(OH)2-D3 [8].
  • The substrate specificity of purified PKC-alpha, -beta and -gamma has been investigated [10].
  • An analysis of the inhibition by UCN-01 and staurosporine of the kinase activity of PKC-alpha and -delta indicated mixed inhibition kinetics [11].
  • UCN-02 was significantly less potent for the inhibition of PKC-alpha, -beta, -gamma, -delta, and -epsilon (IC50 values of 530, 700, 385, 2800, and 1200 nM, respectively) [11].

Anatomical context of PRKCA


Associations of PRKCA with chemical compounds

  • Thus, only PKC-alpha is depleted with a kinetic that corresponds to the loss of feedback inhibition of ATP-stimulated phosphoinositide turnover [12].
  • Protein kinase C activation and IL-8 release were blocked by pretreating BECs with 1 microM calphostin C or 100 nM of the PKC alpha-specific inhibitor, Go 6976 [13].
  • These observations showed that the restoration of the response to bradykinin corresponds to the loss of PKC-epsilon, whereas the restoration of the histamine response corresponds to the loss of PKC-alpha [16].
  • By using selective inhibitors, we observed that depolarization-induced ERK phosphorylation completely depended on protein kinase C-alpha (PKC-alpha), but not on Ca2+/calmodulin-dependent protein kinase nor cyclic AMP-dependent protein kinase [17].
  • Consistent with the need for phosphorylation in this region, an intrinsically active PKC alpha could be produced in bacteria by exchanging Thr-495 for a glutamic acid residue [18].

Regulatory relationships of PRKCA

  • Furthermore, we employed adenoviral PKC-alpha and found that weak PMA stimulation (5 ng/ml) enhanced ERK1/2 activation and MMP-9 secretion in these cells [19].

Other interactions of PRKCA

  • While PKC-alpha and -beta are indistinguishable in their phosphorylation of these peptides, PKC-gamma shows a distinct specificity profile for these synthetic substrates [10].
  • Thus, deregulation of PKC alpha, i.e. by increasing its expression levels in specific cells may affect, in turn the expression of cell surface receptors including the EGF receptor [15].
  • The data indicate that prolonged activation of PKC-alpha, maintained by a translation-dependent pool of PKC-alpha protein, mediates TNF-alpha-induced increases in endothelial permeability in PEM [20].
  • PEM lysates were analyzed for PKC-alpha mRNA (Northern cDNA blot), protein (Western immunoblot), and activity (translocation and phosphorylation of myristoylated arginine-rich C kinase substrate) [20].
  • Basal expression of SNAP-25 was also modified by the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate, but not by Gö6976, a PKC-alpha inhibitor, suggesting that the Ca(2+)-insensitive PKC-epsilon isoform control basal expression of SNAP-25 in these cells [21].

Analytical, diagnostic and therapeutic context of PRKCA


  1. Protein kinase C in galactosemic and tolrestat-treated lens epithelial cells. Gonzalez, K., Udovichenko, I., Cunnick, J., Takemoto, D.J. Curr. Eye Res. (1993) [Pubmed]
  2. Overexpression of protein kinase C alpha and beta1 has distinct effects on bovine aortic endothelial cell growth. Rosales, O.R., Isales, C.M., Bhargava, J. Cell. Signal. (1998) [Pubmed]
  3. Changes associated with tyrosine phosphorylation during short-term hypoxia in retinal microvascular endothelial cells in vitro. Koroma, B.M., de Juan, E. J. Cell. Biochem. (1995) [Pubmed]
  4. An immunohistochemical study of protein kinase C in the bovine retina. Shin, T., Kim, S., Ahn, M., Kim, H. J. Vet. Med. Sci. (2006) [Pubmed]
  5. Protein kinase C and regulation of the local competence of Xenopus ectoderm. Otte, A.P., Kramer, I.M., Durston, A.J. Science (1991) [Pubmed]
  6. Characterization of vascular endothelial growth factor's effect on the activation of protein kinase C, its isoforms, and endothelial cell growth. Xia, P., Aiello, L.P., Ishii, H., Jiang, Z.Y., Park, D.J., Robinson, G.S., Takagi, H., Newsome, W.P., Jirousek, M.R., King, G.L. J. Clin. Invest. (1996) [Pubmed]
  7. Yeast phenotype classifies mammalian protein kinase C cDNA mutants. Riedel, H., Su, L., Hansen, H. Mol. Cell. Biol. (1993) [Pubmed]
  8. 1,25-Dihydroxyvitamin D3 translocates protein kinase C beta to nucleus and enhances plasma membrane association of protein kinase C alpha in renal epithelial cells. Simboli-Campbell, M., Gagnon, A., Franks, D.J., Welsh, J. J. Biol. Chem. (1994) [Pubmed]
  9. Identification of the phosphorylated region responsible for the permissive activation of protein kinase C. Cazaubon, S.M., Parker, P.J. J. Biol. Chem. (1993) [Pubmed]
  10. Studies on the primary sequence requirements for PKC-alpha, -beta 1 and -gamma peptide substrates. Marais, R.M., Nguyen, O., Woodgett, J.R., Parker, P.J. FEBS Lett. (1990) [Pubmed]
  11. Differential inhibition of protein kinase C isozymes by UCN-01, a staurosporine analogue. Seynaeve, C.M., Kazanietz, M.G., Blumberg, P.M., Sausville, E.A., Worland, P.J. Mol. Pharmacol. (1994) [Pubmed]
  12. Feedback regulation of extracellular ATP-stimulated phosphoinositide hydrolysis by protein kinase C-alpha in bovine glomerular endothelial cells. Huwiler, A., Briner, V.A., Fabbro, D., Pfeilschifter, J. Kidney Int. (1997) [Pubmed]
  13. Malondialdehyde-acetaldehyde-adducted bovine serum albumin activates protein kinase C and stimulates interleukin-8 release in bovine bronchial epithelial cells. Wyatt, T.A., Kharbanda, K.K., Tuma, D.J., Sisson, J.H. Alcohol (2001) [Pubmed]
  14. Selected isozymes of PKC contribute to augmented growth of fetal and neonatal bovine PA adventitial fibroblasts. Das, M., Stenmark, K.R., Ruff, L.J., Dempsey, E.C. Am. J. Physiol. (1997) [Pubmed]
  15. Overexpression of protein kinase C alpha-subtype in Swiss/3T3 fibroblasts causes loss of both high and low affinity receptor numbers for epidermal growth factor. Eldar, H., Zisman, Y., Ullrich, A., Livneh, E. J. Biol. Chem. (1990) [Pubmed]
  16. Differential regulation of histamine- and bradykinin-stimulated phospholipase C in adrenal chromaffin cells: evidence for involvement of different protein kinase C isoforms. Sena, C.M., Rosário, L.M., Parker, P.J., Patel, V., Boarder, M.R. J. Neurochem. (1996) [Pubmed]
  17. Depolarization-induced ERK phosphorylation depends on the cytosolic Ca2+ level rather than on the Ca2+ channel subtype of chromaffin cells. Mendoza, I.E., Schmachtenberg, O., Tonk, E., Fuentealba, J., Díaz-Raya, P., Lagos, V.L., García, A.G., Cárdenas, A.M. J. Neurochem. (2003) [Pubmed]
  18. Threonine-497 is a critical site for permissive activation of protein kinase C alpha. Cazaubon, S., Bornancin, F., Parker, P.J. Biochem. J. (1994) [Pubmed]
  19. Protein kinase C-alpha activation by phorbol ester induces secretion of gelatinase B/MMP-9 through ERK 1/2 pathway in capillary endothelial cells. Park, M.J., Park, I.C., Lee, H.C., Woo, S.H., Lee, J.Y., Hong, Y.J., Rhee, C.H., Lee, Y.S., Lee, S.H., Shim, B.S., Kuroki, T., Hong, S.I. Int. J. Oncol. (2003) [Pubmed]
  20. Protein kinase C-alpha mediates endothelial barrier dysfunction induced by TNF-alpha. Ferro, T., Neumann, P., Gertzberg, N., Clements, R., Johnson, A. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) [Pubmed]
  21. Distinct protein kinases regulate SNAP-25 expression in chromaffin cells. Montiel, C., Mendoza, I., García, C.J., Awad, Y., García-Olivares, J., Solís-Garrido, L.M., Lara, H., García, A.G., Cárdenas, A.M. J. Neurosci. Res. (2003) [Pubmed]
  22. Immunocytochemical expression and localization of protein kinase C in bovine aortic endothelial cells. Rosales, O.R., Isales, C., Nathanson, M., Sumpio, B.E. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  23. Translocation of PKC isoforms in bovine aortic smooth muscle cells exposed to strain. Han, O., Takei, T., Basson, M., Sumpio, B.E. J. Cell. Biochem. (2001) [Pubmed]
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