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Gene Review

Prkce  -  protein kinase C, epsilon

Rattus norvegicus

Synonyms: Pkce, Protein kinase C epsilon type, nPKC-epsilon
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Disease relevance of Prkce

  • We have analyzed phosphatidylserine-dependent Ca2+ binding to fusion proteins expressed in Escherichia coli that carry various modifications in the regulatory region of cPKC beta 1 or nPKC epsilon [1].
  • The results suggest that (1) alpha1-adrenoceptor stimulation limits ischemic acidosis, (2) alpha1-adrenergic stimulated attenuation of ischemic acidosis is PKC dependent, (3) direct nPKC stimulation with SAG does not limit ischemic acidosis, and (4) SAG stimulates nPKC-epsilon isoform activation where alpha1-adrenergic stimulation does not [2].

High impact information on Prkce


Biological context of Prkce


Anatomical context of Prkce

  • In the accompanying study (Borner, C.B., Guadagno, S. N., and Weinstein, I. B. (1992) J. Biol. Chem. 267, 12892-12899) we found that R6 embryo fibroblasts express four isoforms of PKC, cPKC alpha, nPKC epsilon, nPKC delta, and nPKC zeta whose subcellular distribution, activation, and down-regulation are differentially regulated [6].
  • We have recently shown that the reduction in insulin sensitivity of rats fed a high-fat diet is associated with the translocation of the novel protein kinase C epsilon (nPKC epsilon) from cytosolic to particulate fractions in red skeletal muscle and also the downregulation of cytosolic nPKC theta [10].

Associations of Prkce with chemical compounds

  • Placental protein expression of all three cPKC isoforms was downregulated by maternal dexamethasone exposure, whereas placental nPKC-epsilon protein expression and activity was significantly upregulated in a dose-dependent manner [11].

Regulatory relationships of Prkce


Other interactions of Prkce

  • EC50 values for the translocation of nPKC-delta and nPKC-epsilon by BK(1-8) were more than 5 microM [13].
  • 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 [14].

Analytical, diagnostic and therapeutic context of Prkce

  • Northern blot analysis indicated a significant (2.3-fold) increase in the 10 kb transcript of cPKC-alpha, a slight (1.3-fold) increase in that of nPKC-epsilon but no detectable change in that of the remaining isozymes [15].
  • Western blot analysis indicated that growth to confluent density significantly increased the protein levels of cPKC-alpha (11.6-fold), nPKC-delta (5.3-fold), and nPKC-epsilon (22.0-fold) but not aPKC-zeta [15].
  • A novel Ca2(+)-independent PKC, nPKC epsilon, was identified together with two conventional Ca2(+)-dependent PKCs, PKC alpha and beta II by analysis of kinase and phorbol ester-binding activities, immunoblotting using isozyme-specific antibodies, and Northern blotting [14].


  1. Calcium-dependent activation of protein kinase C. The role of the C2 domain in divalent cation selectivity. Luo, J.H., Weinstein, I.B. J. Biol. Chem. (1993) [Pubmed]
  2. Alpha-adrenergic preservation of myocardial pH during ischemia is PKC isoform dependent. Rehring, T.F., Friese, R.S., Cleveland, J.C., Meng, X., Robertson, F.G., Harken, A.H., Bannerjee, A. J. Surg. Res. (1996) [Pubmed]
  3. The role of the calpain-calpastatin system in thyrotropin-releasing hormone-induced selective down-regulation of a protein kinase C isozyme, nPKC epsilon, in rat pituitary GH4C1 cells. Eto, A., Akita, Y., Saido, T.C., Suzuki, K., Kawashima, S. J. Biol. Chem. (1995) [Pubmed]
  4. Activation of novel protein kinases C delta and C epsilon upon mitogenic stimulation of quiescent rat 3Y1 fibroblasts. Ohno, S., Mizuno, K., Adachi, Y., Hata, A., Akita, Y., Akimoto, K., Osada, S., Hirai, S., Suzuki, K. J. Biol. Chem. (1994) [Pubmed]
  5. Overproduction of a Ca(2+)-independent protein kinase C isozyme, nPKC epsilon, increases the secretion of prolactin from thyrotropin-releasing hormone-stimulated rat pituitary GH4C1 cells. Akita, Y., Ohno, S., Yajima, Y., Konno, Y., Saido, T.C., Mizuno, K., Chida, K., Osada, S., Kuroki, T., Kawashima, S. J. Biol. Chem. (1994) [Pubmed]
  6. Expression of four protein kinase C isoforms in rat fibroblasts. Differential alterations in ras-, src-, and fos-transformed cells. Borner, C., Guadagno, S.N., Hsiao, W.W., Fabbro, D., Barr, M., Weinstein, I.B. J. Biol. Chem. (1992) [Pubmed]
  7. Functional divergence of protein kinase C (PKC) family members. PKC gamma differs from PKC alpha and -beta II and nPKC epsilon in its competence to mediate-12-O-tetradecanoyl phorbol 13-acetate (TPA)-responsive transcriptional activation through a TPA-response element. Hata, A., Akita, Y., Suzuki, K., Ohno, S. J. Biol. Chem. (1993) [Pubmed]
  8. Cardiac protein kinase C expression in two models of cardiac hypertrophy associated with an activated cardiac renin-angiotensin system: effects of experimental hyperthyroidism and genetic hypertension (the mRen-2 rat). Fryer, L.G., Holness, M.J., Decock, J.B., Sugden, M.C. J. Endocrinol. (1998) [Pubmed]
  9. A protein kinase C isozyme, nPKC epsilon, is involved in the activation of NF-kappa B by 12-O-tetradecanoylphorbol-13-acetate (TPA) in rat 3Y1 fibroblasts. Hirano, M., Hirai, S., Mizuno, K., Osada, S., Hosaka, M., Ohno, S. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  10. Reversal of chronic alterations of skeletal muscle protein kinase C from fat-fed rats by BRL-49653. Schmitz-Peiffer, C., Oakes, N.D., Browne, C.L., Kraegen, E.W., Biden, T.J. Am. J. Physiol. (1997) [Pubmed]
  11. Possible involvement of PKC isoforms in signalling placental apoptosis in intrauterine growth retardation. Sugden, M.C., Langdown, M.L. Mol. Cell. Endocrinol. (2001) [Pubmed]
  12. Expression of four protein kinase C isoforms in rat fibroblasts. Distinct subcellular distribution and regulation by calcium and phorbol esters. Borner, C., Guadagno, S.N., Fabbro, D., Weinstein, I.B. J. Biol. Chem. (1992) [Pubmed]
  13. Stimulation of phosphatidylinositol hydrolysis, protein kinase C translocation, and mitogen-activated protein kinase activity by bradykinin in rat ventricular myocytes: dissociation from the hypertrophic response. Clerk, A., Gillespie-Brown, J., Fuller, S.J., Sugden, P.H. Biochem. J. (1996) [Pubmed]
  14. 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]
  15. Regulation of expression and activity of four PKC isozymes in confluent and mechanically stimulated UMR-108 osteoblastic cells. Geng, W.D., Boskovic, G., Fultz, M.E., Li, C., Niles, R.M., Ohno, S., Wright, G.L. J. Cell. Physiol. (2001) [Pubmed]
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