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Gene Review

PKC  -  protein kinase C beta 1

Sus scrofa

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Disease relevance of PKC

  • The protein kinase C (PKC) pathway has recently been recognized as an important mechanism in the development of diabetic complications including cardiomyopathy and angiopathy [1].
  • We now determine the role of protein kinase C (PKC) in ethanol's protective effect against ischemia-reperfusion injury [2].
  • Currently at least 11 protein kinase C (PKC) isoforms have been identified and may play different roles in cell signaling pathways leading to changes in cardiac contractility, the hypertrophic response, and tolerance to myocardial ischemia [3].
  • Permeabilization in a cerebral endothelial barrier model by pertussis toxin involves the PKC effector pathway and is abolished by elevated levels of cAMP [4].
  • Before ischemia, hearts were either untreated or treated with sevoflurane (APC) in the absence or presence of the nonspecific PKC inhibitor chelerythrine, the PKC-delta inhibitor PP101, or the PKC-epsilon inhibitor PP149 [5].

High impact information on PKC


Chemical compound and disease context of PKC


Biological context of PKC

  • Upregulation of PKC genes and isozymes in cardiovascular tissues during early stages of experimental diabetes [1].
  • Attenuation of CaMKII activity by PKC showed strong similarity to the downregulation of CaMKII by basal autophosphorylation [11].
  • (5) Since both kinase modulators, TPA and KN-62, affected no divergent signal transduction pathways in the parietal cell, an in vitro model has been used to study if PKC directly targets CaMKII [11].
  • Protein kinase C (PKC) is activated at the cell membrane by interacting with both the acidic lipid phosphatidylserine and the second messenger diacylglycerol [12].
  • We conclude that in the adult heart, LV dilation produced stretch-mediated activation of phospholipase C, which resulted in PI hydrolysis and PKC epsilon activation in part by stimulation of the local renin angiotensin system [13].

Anatomical context of PKC

  • We conclude that an increase in extracellular glucose leads to a rapid dose-dependent increase in endothelial cell permeability via the activiation of PKC and that this effect is mediated by the PKC isoform alpha [14].
  • Modulation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) disrupts the cell-cell junctions of the epithelial cell line LLC-PK1 [15].
  • These results indicate that the alpha isoform of PKC is at least one of the isoforms that regulate tight junctions and other cell-cell junctions of LLC-PK1 epithelia [15].
  • CaMKII purified from parietal cell-containing gastric mucosa of pig, was transphosphorylated by purified cPKC containing PKC-alpha up to 1.8 mol P(i) per mol CaMKII in vitro [11].
  • (1) The phorbolester 12-O-tetradecanoyl phorbol-13-acetate (TPA), an activator of protein kinase C (PKC), inhibits cholinergic stimulation of gastric acid secretion [11].

Associations of PKC with chemical compounds

  • In this study we assessed quantitatively the mRNA and protein expression profiles of PKC isozymes in the heart and vascular tissues from streptozotocin-induced diabetic pigs [1].
  • High glucose activates protein kinase C (PKC), a family of kinases vital to intracellular signaling [14].
  • To examine the role of specific PKC isoforms in this process we have created modified LLC-PK1 subclones that express wild-type and dominant negative versions of PKC-alpha under control of the tetracycline-responsive expression system [15].
  • (3) Gö 6976, an inhibitor of calcium-dependent PKC, concentration-dependently antagonized the inhibitory effect of TPA, and, therefore, revealed the action of PKC-alpha on carbachol-induced acid secretion in rabbit parietal cells [11].
  • Calphostin C, a PKC inhibitor, abrogated the FB(1)-induced translocation of PKCalpha [16].

Physical interactions of PKC


Regulatory relationships of PKC

  • However, it is presently not clear whether PKC is activating the same population of channels as PKA or a separate class of Cl- channels. even though the regulatory (R) domain of CFTR is known to contain consensus phosphorylation sites for both PKA and PKC [18].
  • In contrast, the IGFBP-5 expression induced by forskolin was unaffected by PKC down-regulation or inhibition, suggesting that PKC activation is required for the IGF-regulated but not the cAMP-regulated events [19].
  • When these reductions of connexin-43 were blocked by protein kinase C (PKC) or phosphatidylinositol (PI) 3-kinase inhibitor, networks of filamentous bivalents (i.e., advanced chromosomal status) were undetectable in the germinal vesicle of the oocyte [20].
  • These results are consistent with the view that activation of PKC provides at least one intracellular mechanism that regulates relaxin secretion by porcine luteal cells [21].
  • Finally, the partial inhibitory effect of a protein kinase C (PKC) inhibitor, bisindolylmaleimide, on EGF-stimulated LDH A mRNA supports a partial involvement of PKC in the action of the growth factor [22].

Other interactions of PKC

  • By contrast, phorbol myristate acetate (PMA, 200 nM), a potent activator of PKC, induced a relocalization of PKC alpha from the C to the PM [23].
  • (6) The phosphotransferase activity of the purified CaMKII was in vitro inhibited after transphosphorylation by PKC if calmodulin was absent during transphosphorylation [11].
  • The involvement of protein kinase C (PKC) in vasopressin-induced effects on renal water reabsorption is still unresolved [23].
  • Leptin led to a nitric oxide (NO) synthase (NOS)-specific, dose-dependent increase in NO production from PBMCs because leptin-induced NO release was blocked by the addition of the NOS inhibitor Nomega-Nitro-l-arginine methyl ester and protein kinase C (PKC) inhibitor calphostin C [24].
  • Treatment of the arteries with phorbol 12-myristate 13-acetate, a potent stimulator of PKC, induced ICAM-1 expression and enhanced the endothelial adhesiveness to PMNs and PMN-induced EDR impairment, mimicking the effects of Ox-LDL [25].

Analytical, diagnostic and therapeutic context of PKC


  1. Upregulation of PKC genes and isozymes in cardiovascular tissues during early stages of experimental diabetes. Guo, M., Wu, M.H., Korompai, F., Yuan, S.Y. Physiol. Genomics (2003) [Pubmed]
  2. Activation of epsilon protein kinase C correlates with a cardioprotective effect of regular ethanol consumption. Miyamae, M., Rodriguez, M.M., Camacho, S.A., Diamond, I., Mochly-Rosen, D., Figueredo, V.M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Responses of cardiac protein kinase C isoforms to distinct pathological stimuli are differentially regulated. Takeishi, Y., Jalili, T., Ball, N.A., Walsh, R.A. Circ. Res. (1999) [Pubmed]
  4. Permeabilization in a cerebral endothelial barrier model by pertussis toxin involves the PKC effector pathway and is abolished by elevated levels of cAMP. Brückener, K.E., el Bayâ, A., Galla, H.J., Schmidt, M.A. J. Cell. Sci. (2003) [Pubmed]
  5. Reactive oxygen species precede the epsilon isoform of protein kinase C in the anesthetic preconditioning signaling cascade. Novalija, E., Kevin, L.G., Camara, A.K., Bosnjak, Z.J., Kampine, J.P., Stowe, D.F. Anesthesiology (2003) [Pubmed]
  6. Increased Kit/SCF receptor induced mitogenicity but abolished cell motility after inhibition of protein kinase C. Blume-Jensen, P., Siegbahn, A., Stabel, S., Heldin, C.H., Rönnstrand, L. EMBO J. (1993) [Pubmed]
  7. Calcium antagonists ameliorate ischemia-induced endothelial cell permeability by inhibiting protein kinase C. Hempel, A., Lindschau, C., Maasch, C., Mahn, M., Bychkov, R., Noll, T., Luft, F.C., Haller, H. Circulation (1999) [Pubmed]
  8. Mechanism of N-formyl-methionyl-leucyl-phenylalanine- and platelet-activating factor-induced arachidonic acid release in guinea pig alveolar macrophages: involvement of a GTP-binding protein and role of protein kinase A and protein kinase C. Kadiri, C., Cherqui, G., Masliah, J., Rybkine, T., Etienne, J., Béréziat, G. Mol. Pharmacol. (1990) [Pubmed]
  9. Pertussis toxin activates L-arginine uptake in pulmonary endothelial cells through downregulation of PKC-alpha activity. Zharikov, S.I., Krotova, K.Y., Belayev, L., Block, E.R. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
  10. Protein kinase Cs and tyrosine kinases in permissive action of prostacyclin on cerebrovascular regulation in newborn pigs. Rama, G.P., Parfenova, H., Leffler, C.W. Pediatr. Res. (1997) [Pubmed]
  11. Protein kinase C-alpha attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells. Fährmann, M., Kaufhold, M., Pfeiffer, A.F., Seidler, U. Br. J. Pharmacol. (2003) [Pubmed]
  12. Replacement of Ser657 of protein kinase C-alpha by alanine leads to premature down regulation after phorbol-ester-induced translocation to the membrane. Gysin, S., Imber, R. Eur. J. Biochem. (1996) [Pubmed]
  13. Left ventricular stretch stimulates angiotensin II--mediated phosphatidylinositol hydrolysis and protein kinase C epsilon isoform translocation in adult guinea pig hearts. Paul, K., Ball, N.A., Dorn, G.W., Walsh, R.A. Circ. Res. (1997) [Pubmed]
  14. High glucose concentrations increase endothelial cell permeability via activation of protein kinase C alpha. Hempel, A., Maasch, C., Heintze, U., Lindschau, C., Dietz, R., Luft, F.C., Haller, H. Circ. Res. (1997) [Pubmed]
  15. Protein kinase C-alpha activity modulates transepithelial permeability and cell junctions in the LLC-PK1 epithelial cell line. Rosson, D., O'Brien, T.G., Kampherstein, J.A., Szallasi, Z., Bogi, K., Blumberg, P.M., Mullin, J.M. J. Biol. Chem. (1997) [Pubmed]
  16. Selective and transient activation of protein kinase C alpha by fumonisin B1, a ceramide synthase inhibitor mycotoxin, in cultured porcine renal cells. Gopee, N.V., Sharma, R.P. Life Sci. (2004) [Pubmed]
  17. Activation of muscarinic receptors in porcine airway smooth muscle elicits a transient increase in phospholipase D activity. Mamoon, A.M., Smith, J., Baker, R.C., Farley, J.M. J. Biomed. Sci. (1999) [Pubmed]
  18. Unitary chloride channels activated by protein kinase C in guinea pig ventricular myocytes. Collier, M.L., Hume, J.R. Circ. Res. (1995) [Pubmed]
  19. Down-regulation of protein kinase C inhibits insulin-like growth factor I-induced vascular smooth muscle cell proliferation, migration, and gene expression. Yano, K., Bauchat, J.R., Liimatta, M.B., Clemmons, D.R., Duan, C. Endocrinology (1999) [Pubmed]
  20. Dynamic changes of connexin-43, gap junctional protein, in outer layers of cumulus cells are regulated by PKC and PI 3-kinase during meiotic resumption in porcine oocytes. Shimada, M., Maeda, T., Terada, T. Biol. Reprod. (2001) [Pubmed]
  21. Stimulatory effect of phorbol diester on relaxin release by porcine luteal cells in culture. Taylor, M.J., Clark, C.L. Biol. Reprod. (1988) [Pubmed]
  22. Epidermal growth factor regulates glucose metabolism through lactate dehydrogenase A messenger ribonucleic acid expression in cultured porcine Sertoli cells. Boussouar, F., Benahmed, M. Biol. Reprod. (1999) [Pubmed]
  23. Is protein kinase C alpha (PKC alpha) involved in vasopressin-induced effects on LLC-PK1 pig kidney cells? Dibas, A., Mia, A.J., Yorio, T. Biochem. Mol. Biol. Int. (1996) [Pubmed]
  24. Leptin induces growth hormone secretion from peripheral blood mononuclear cells via a protein kinase C- and nitric oxide-dependent mechanism. Dixit, V.D., Mielenz, M., Taub, D.D., Parvizi, N. Endocrinology (2003) [Pubmed]
  25. Lysophosphatidylcholine in oxidized low-density lipoprotein increases endothelial susceptibility to polymorphonuclear leukocyte-induced endothelial dysfunction in porcine coronary arteries. Role of protein kinase C. Sugiyama, S., Kugiyama, K., Ohgushi, M., Fujimoto, K., Yasue, H. Circ. Res. (1994) [Pubmed]
  26. SLC26 transporters and the inhibitory control of pancreatic ductal bicarbonate secretion. Hegyi, P., Rakonczay, Z., Tiszlavicz, L., Varr??, A., T??th, A., R??cz, G., Varga, G., Gray, M.A., Argent, B.E. Novartis Found. Symp. (2006) [Pubmed]
  27. Protein kinase-dependent Cl- currents in feline ventricular myocytes. Zhang, K., Barrington, P.L., Martin, R.L., Ten Eick, R.E. Circ. Res. (1994) [Pubmed]
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