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Gene Review

Prkcg  -  protein kinase C, gamma

Rattus norvegicus

Synonyms: PKC, PKC-gamma, PKCI, Pkcc, Pkcg, ...
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Disease relevance of Prkcc


Psychiatry related information on Prkcc

  • We conclude that the simultaneous inhibition of PI3K and PKC can induce GSK-3 overactivation, and further strengthen and prolong the Alzheimer-like tau hyperphosphorylation in N2a cells, suggesting the establishment of a cell model with early pathological events of Alzheimer's disease [6].
  • Since RACK1 facilitates the PKC substrate accessibility, driving its cellular localization, the coordinate regulation of the PKC/RACK system by morphine could be a relevant molecular mechanism in opiate addiction [7].
  • Thus, these results directly suggest that activation of PKC pathways in a specific hippocampal area alters rat auditory discrimination reversal learning [8].
  • Restoration of spontaneous exploratory behaviors with an intrathecal NMDA receptor antagonist or a PKC inhibitor in rats with acute pancreatitis [9].
  • That similar patterns of PKC translocation are observed in experimental models of ischaemic preconditioning and genetic PKC manipulation provide evidence for a dose-dependent cardioprotective phenotype induced by physical activity [10].

High impact information on Prkcc

  • These cell lines contain a 20- to 53-fold increase in PKC activity and exhibit dramatically enhanced morphologic changes following exposure to the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) [11].
  • Thus, the mere overproduction of a single form of PKC is sufficient to confer multiple growth abnormalities in rat fibroblasts [11].
  • Transfection of NIH 3T3 cells with plasmids containing rat brain protein kinase C-I (PKC-I) cDNA controlled by strong viral promoter/enhancer elements led to PKC-I gene expression as assessed by Northern analysis, cellular binding of phorbol ester, immunoblotting of cellular PKC, and membrane-associated PKC activity [12].
  • The protein kinase C (PKC) family of serine/threonine kinases functions downstream of nearly all membrane-associated signal transduction pathways [13].
  • Moreover, the pro-inflammatory peptide, bradykinin, and the putative endogenous ligand, anandamide, respectively induced and enhanced VR activity, in a PKC-dependent manner [14].

Chemical compound and disease context of Prkcc


Biological context of Prkcc


Anatomical context of Prkcc

  • PKC induced a rapid delivery of functional NMDARs to the cell surface and increased surface NR1 immunofluorescence in Xenopus oocytes expressing NMDARs [20].
  • PKC epsilon was present in brain, kidney, and pancreas, whereas PKC epsilon' was present predominantly in brain [21].
  • The pattern of protein kinase C (PKC) isotype expression in whole extracts of dispersed, freshly isolated adult rat ventricular myocytes and adult rat heart ventricle was examined by immunoblot analysis using antisera specific for PKC-alpha, -beta 1, -gamma, -delta, -epsilon, -zeta, or -eta isotypes [1].
  • All PKC isotypes were detectable in appropriate positive control extracts (brain or certain cultured cell lines) [1].
  • We investigated the ET receptor subtype involved in mitogenic signaling in glomerular mesangial cells and the role of protein kinase C (PKC) and protein tyrosine kinase (PTK) activity [23].

Associations of Prkcc with chemical compounds

  • PKC was sequentially purified from rat brain, and the calcium-dependent forms were finally resolved by hydroxyapatite chromatography [21].
  • Serine residue 890 in the C1 cassette is a primary target of PKC phosphorylation and a critical residue in receptor clustering at the membrane [24].
  • On exposure of the cardiomyocytes to 1 microM phorbol 12-myristate 13-acetate (PMA), PKC-epsilon undergoes a rapid (< 30 seconds), sustained (at least 60 minutes), and virtually complete association with the Triton X-100-soluble membrane fraction [1].
  • PKC-epsilon also translocated on exposure of cardiomyocytes to 50 microM epinephrine or 100 nM endothelin-1 [1].
  • The effects of high glucose and protein kinase C (PKC) activation on platelet-derived growth factor (PDGF)-BB and of ET-1 expression in the retina of streptozotocin (STZ)-induced diabetic rats and bovine retinal pericytes (BRPC) were examined [2].

Physical interactions of Prkcc

  • Endothelin (1 x 10(-6) M) also increased the plasma membrane bound protein kinase C (PKC) activity by 4 fold [25].
  • Taken together, our results indicate that PKC interacts in vivo with calreticulin and suggest that they can operate in common signalling pathways [26].

Enzymatic interactions of Prkcc

  • The results show that PKC alpha phosphorylates preferentially S896 and PKC gamma preferentially S890 [27].
  • We now demonstrate that PKA and various PKC isoforms phosphorylate the NMDA receptor in vitro [28].
  • These data demonstrate that TnI and C-protein are phosphorylated in myocardial cells by both PKA and PKC, resulting in different functional consequences in each case [29].
  • Cytosolic PKC-dependent histone-phosphorylating enzyme activity and PKC-beta immunoreactivity of both adipocytes and soleus muscles increased progressively with age (or weight) in rats weighing less than 400 g [30].

Regulatory relationships of Prkcc


Other interactions of Prkcc

  • PKC alpha, -beta and -gamma isoenzymes separated by hydroxylapatite chromatography all cross-reacted with anti-PKC zeta [35].
  • A general PKC inhibitor, GF109203X, suppressed PDGF-BB's induction of ET-1 mRNA [2].
  • A highly specific PKC beta inhibitor, LY379196, blocked dopamine efflux that was stimulated by either amphetamine or the PKC activator, 12-O-tetradecanoylphorbol-13-acetate [36].
  • The purpose of this study was to identify the specific PKC isozymes mediating the effects of HG on MC extracellular signal-regulated protein kinase (ERK1/2) signaling and alpha1(IV) collagen expression in response to ET-1 [37].
  • Therefore, we investigated the signaling pathway for Ca(2+)- and PKC-dependent NF-kappaB activation, inducible nitric-oxide synthase expression, and tumor necrosis factor-alpha (TNF-alpha) production in LPS-stimulated rat peritoneal macrophages [38].

Analytical, diagnostic and therapeutic context of Prkcc


  1. Characterization of protein kinase C isotype expression in adult rat heart. Protein kinase C-epsilon is a major isotype present, and it is activated by phorbol esters, epinephrine, and endothelin. Bogoyevitch, M.A., Parker, P.J., Sugden, P.H. Circ. Res. (1993) [Pubmed]
  2. Role of protein kinase C on the expression of platelet-derived growth factor and endothelin-1 in the retina of diabetic rats and cultured retinal capillary pericytes. Yokota, T., Ma, R.C., Park, J.Y., Isshiki, K., Sotiropoulos, K.B., Rauniyar, R.K., Bornfeldt, K.E., King, G.L. Diabetes (2003) [Pubmed]
  3. Characterization of the 5'-flanking region of the rat protein kinase C gamma gene. Chen, K.H., Widen, S.G., Wilson, S.H., Huang, K.P. J. Biol. Chem. (1990) [Pubmed]
  4. Protein kinase C-gamma and calcium/calmodulin-dependent protein kinase II-alpha are persistently translocated to cell membranes of the rat brain during and after middle cerebral artery occlusion. Matsumoto, S., Shamloo, M., Matsumoto, E., Isshiki, A., Wieloch, T. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
  5. Chronic exposure to ammonia induces isoform-selective alterations in the intracellular distribution and NMDA receptor-mediated translocation of protein kinase C in cerebellar neurons in culture. Giordano, G., Sanchez-Perez, A.M., Burgal, M., Montoliu, C., Costa, L.G., Felipo, V. J. Neurochem. (2005) [Pubmed]
  6. Prolonged Alzheimer-like tau hyperphosphorylation induced by simultaneous inhibition of phosphoinositol-3 kinase and protein kinase C in N2a cells. Xu, G.G., Deng, Y.Q., Liu, S.J., Li, H.L., Wang, J.Z. Acta Biochim. Biophys. Sin. (Shanghai) (2005) [Pubmed]
  7. Parallel modulation of receptor for activated C kinase 1 and protein kinase C-alpha and beta isoforms in brains of morphine-treated rats. Escribá, P.V., García-Sevilla, J.A. Br. J. Pharmacol. (1999) [Pubmed]
  8. Enhanced auditory reversal learning by genetic activation of protein kinase C in small groups of rat hippocampal neurons. Neill, J.C., Sarkisian, M.R., Wang, Y., Liu, Z., Yu, L., Tandon, P., Zhang, G., Holmes, G.L., Geller, A.I. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  9. Restoration of spontaneous exploratory behaviors with an intrathecal NMDA receptor antagonist or a PKC inhibitor in rats with acute pancreatitis. Zhang, L., Zhang, X., Westlund, K.N. Pharmacol. Biochem. Behav. (2004) [Pubmed]
  10. Dose-dependent effects of acute exercise on PKC levels in rat heart: is PKC the heart's prophylactic? Carson, L.D., Korzick, D.H. Acta Physiol. Scand. (2003) [Pubmed]
  11. Overproduction of protein kinase C causes disordered growth control in rat fibroblasts. Housey, G.M., Johnson, M.D., Hsiao, W.L., O'Brian, C.A., Murphy, J.P., Kirschmeier, P., Weinstein, I.B. Cell (1988) [Pubmed]
  12. Altered growth regulation and enhanced tumorigenicity of NIH 3T3 fibroblasts transfected with protein kinase C-I cDNA. Persons, D.A., Wilkison, W.O., Bell, R.M., Finn, O.J. Cell (1988) [Pubmed]
  13. 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]
  14. Induction of vanilloid receptor channel activity by protein kinase C. Premkumar, L.S., Ahern, G.P. Nature (2000) [Pubmed]
  15. Inhibition of protein kinase C reduces ischemia-induced tyrosine phosphorylation of the N-methyl-d-aspartate receptor. Cheung, H.H., Teves, L., Wallace, M.C., Gurd, J.W. J. Neurochem. (2003) [Pubmed]
  16. 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]
  17. Dissociation of vasoconstrictor-stimulated basic fibroblast growth factor expression from hypertrophic growth in cultured vascular smooth muscle cells. Relevant roles of protein kinase C. Ali, S., Becker, M.W., Davis, M.G., Dorn, G.W. Circ. Res. (1994) [Pubmed]
  18. Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C. Mao, J., Price, D.D., Mayer, D.J. J. Neurosci. (1994) [Pubmed]
  19. Regulation of NMDA receptor phosphorylation by alternative splicing of the C-terminal domain. Tingley, W.G., Roche, K.W., Thompson, A.K., Huganir, R.L. Nature (1993) [Pubmed]
  20. Protein kinase C modulates NMDA receptor trafficking and gating. Lan , J.Y., Skeberdis, V.A., Jover, T., Grooms, S.Y., Lin, Y., Araneda, R.C., Zheng, X., Bennett, M.V., Zukin, R.S. Nat. Neurosci. (2001) [Pubmed]
  21. 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]
  22. Protein kinase C modulation of recombinant NMDA receptor currents: roles for the C-terminal C1 exon and calcium ions. Logan, S.M., Rivera, F.E., Leonard, J.P. J. Neurosci. (1999) [Pubmed]
  23. Protein kinase C and protein tyrosine kinase activity contribute to mitogenic signaling by endothelin-1. Cross-talk between G protein-coupled receptors and pp60c-src. Simonson, M.S., Herman, W.H. J. Biol. Chem. (1993) [Pubmed]
  24. Protein kinase C potentiation of N-methyl-D-aspartate receptor activity is not mediated by phosphorylation of N-methyl-D-aspartate receptor subunits. Zheng, X., Zhang, L., Wang, A.P., Bennett, M.V., Zukin, R.S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  25. Endothelin inhibits the atrial natriuretic factor stimulated cGMP production by activating the protein kinase C in rat aortic smooth muscle cells. Jaiswal, R.K. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  26. Characterization of calreticulin as a protein interacting with protein kinase C. Rendón-Huerta, E., Mendoza-Hernández, G., Robles-Flores, M. Biochem. J. (1999) [Pubmed]
  27. 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]
  28. Cyclic AMP-dependent protein kinase and protein kinase C phosphorylate N-methyl-D-aspartate receptors at different sites. Leonard, A.S., Hell, J.W. J. Biol. Chem. (1997) [Pubmed]
  29. Protein kinase C-mediated phosphorylation of troponin I and C-protein in isolated myocardial cells is associated with inhibition of myofibrillar actomyosin MgATPase. Venema, R.C., Kuo, J.F. J. Biol. Chem. (1993) [Pubmed]
  30. Differential effect of aging on protein kinase C activity in rat adipocytes and soleus muscle. Ishizuka, T., Yamamoto, M., Kajita, K., Yasuda, K., Miura, K., Hernandez, H., Farese, R.V. Metab. Clin. Exp. (1993) [Pubmed]
  31. Endothelin-1 stimulates tyrosine phosphorylation of p125 focal adhesion kinase in mesangial cells. Haneda, M., Kikkawa, R., Koya, D., Shikano, T., Sugimoto, T., Togawa, M., Shigeta, Y. J. Am. Soc. Nephrol. (1995) [Pubmed]
  32. ICAM-1 expression on cardiac myocytes and aortic endothelial cells via their specific endothelin receptor subtype. Hayasaki, Y., Nakajima, M., Kitano, Y., Iwasaki, T., Shimamura, T., Iwaki, K. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  33. In vivo expression of classic PKC isoforms in the rat dental follicle as related to tooth eruption. Yao, S., Wise, G. Connect. Tissue Res. (2004) [Pubmed]
  34. Characterization of a rat brain phospholipase D isozyme. Min, D.S., Park, S.K., Exton, J.H. J. Biol. Chem. (1998) [Pubmed]
  35. Identification and characterization of protein kinase C zeta-immunoreactive proteins. Allen, B.G., Andrea, J.E., Walsh, M.P. J. Biol. Chem. (1994) [Pubmed]
  36. Regulation of amphetamine-stimulated dopamine efflux by protein kinase C beta. Johnson, L.A., Guptaroy, B., Lund, D., Shamban, S., Gnegy, M.E. J. Biol. Chem. (2005) [Pubmed]
  37. High glucose-enhanced mesangial cell extracellular signal-regulated protein kinase activation and alpha1(IV) collagen expression in response to endothelin-1: role of specific protein kinase C isozymes. Hua, H., Goldberg, H.J., Fantus, I.G., Whiteside, C.I. Diabetes (2001) [Pubmed]
  38. Ca2+- and Protein Kinase C-dependent Signaling Pathway for Nuclear Factor-{kappa}B Activation, Inducible Nitric-oxide Synthase Expression, and Tumor Necrosis Factor-{alpha} Production in Lipopolysaccharide-stimulated Rat Peritoneal Macrophages. Zhou, X., Yang, W., Li, J. J. Biol. Chem. (2006) [Pubmed]
  39. 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]
  40. Individual differences in spatial memory among aged rats are related to hippocampal PKCgamma immunoreactivity. Colombo, P.J., Gallagher, M. Hippocampus. (2002) [Pubmed]
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