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Gene Review

Prkcg  -  protein kinase C, gamma

Mus musculus

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


Psychiatry related information on Prkcc


High impact information on Prkcc

  • PKC gamma is highly expressed in Purkinje cells (PCs) but not in other types of neurons in the cerebellum [8].
  • In adult mutant mice deficient in PKC gamma, we found that 41% of PCs are still innervated by multiple climbing fibers, while other aspects of the cerebellum including the morphology and excitatory synaptic transmission of PCs appear normal [8].
  • Modified hippocampal long-term potentiation in PKC gamma-mutant mice [9].
  • Here, mice that lack protein kinase C gamma (PKCgamma) displayed normal responses to acute pain stimuli, but they almost completely failed to develop a neuropathic pain syndrome after partial sciatic nerve section, and the neurochemical changes that occurred in the spinal cord after nerve injury were blunted [10].
  • Also, PKCgamma was shown to be restricted to a small subset of dorsal horn neurons, thus identifying a potential biochemical target for the prevention and therapy of persistent pain [10].

Chemical compound and disease context of Prkcc


Biological context of Prkcc

  • The mouse and rat PKC-gamma nt and deduced amino acid sequences share 97 and 100% identity, respectively [13].
  • Here, we report the cDNA sequence encoding mouse PKC-gamma isolated from a C57BL/6 brain cDNA library [13].
  • The region containing nucleotides 87 upstream from the transcriptional initiation site was shown to silence CAT activity in Balb/c3T3 cells, in which mRNA of PKC gamma was not detected, suggesting that this region might contain a transcriptional regulatory element for the cell type-specific expression of the PKC gamma gene [14].
  • These findings suggest that the loss of the PKC gamma gene may protect the functional ORL-1 and mu-opioid receptors from degradation by phosphorylation in the mouse pons/medulla [15].
  • To investigate the contribution of the PKC gamma isoform of protein kinase C (PKC) in neurochemical pathways regulating anxiety, mice lacking the gene encoding PKC gamma were tested with heterozygote and wild-type littermates in three approach-avoidance tests of anxiety [16].

Anatomical context of Prkcc

  • PKCgamma is a protein kinase C (PKC) isoform that is expressed in the central nervous system (CNS) [17].
  • These findings present a link between vacuole formation and loss of dendrites in Purkinje cells of SCA1 mice and indicate that altered somatodendritic membrane trafficking and loss of proteins including PKCgamma, are a part of the neuronal dysfunction in SCA1 transgenic mice [18].
  • In this study, we investigated the spatio-temporal distribution of conventional protein kinases C (cPKC) isoforms PKC-alpha, PKC-betaI, PKC-betaII and PKC-gamma in mouse oocytes [19].
  • Fifteen minutes following topical treatment with a tumor promoting dose of TPA (3.4 nmol), the activities of PKC beta and PKC gamma decreased in the epidermal cytosol to 30% and 50% of control values, respectively, while these activities were increased in the epidermal particulate fraction by approximately 50% [20].
  • A null mutation of the gamma isoform of protein kinase C (PKCgamma KO [knockout]), as well as an inbred mouse strain, 129S6, also does not manifest behavioral signs of neuropathic pain following peripheral nerve injury [2].

Associations of Prkcc with chemical compounds

  • We tested a line of null mutant mice that lacks the gamma isoform of PKC (PKC gamma) to determine the role of this brain-specific isoenzyme in ethanol sensitivity [21].
  • When the cells were treated with retinoic acid either alone or in the presence of cAMP for 120 h, PKC alpha mRNA and protein levels increased, whereas those of PKC beta and PKC gamma became undetectable [22].
  • To assess the contribution of PKC gamma to this process, we studied the responses of wild-type and mutant mice to an intraplantar injection of formalin (a model of persistent pain) following chronic morphine treatment [23].
  • Reduced development of tolerance to the analgesic effects of morphine and clonidine in PKC gamma mutant mice [23].
  • In contrast to results in pyramidal cells from rats or wild-type mice, neither clozapine nor PMA was able to potentiate NMDA-induced currents in the mPFC from the PKCgamma mutant mice [24].

Regulatory relationships of Prkcc

  • Results from the present study indicate that the gene encoding the neuronal-specific gamma subtype of protein kinase C (PKCgamma) influences both ethanol consumption and behavioral impulsivity, a personality characteristic associated with Type II alcoholics, in a pleiotropic manner [25].
  • Together with our previous work on the role of PKCgamma, these data support a model predicting that normal Purkinje cell dendritic growth is mainly regulated by the PKCgamma-isoform, which is highly activated by developmental processes [26].
  • Concomitantly, PKCgamma induced a dramatic down-regulation of E-cadherin protein levels and its localization to cell-cell junctions [27].

Other interactions of Prkcc

  • The Ca2+-dependent isoenzymes, PKC alpha and PKC betaII, showed significant expression on GD 12.0, which gradually decreased through GD 14.5, whereas PKC betaI and PKC gamma were negligible throughout [28].
  • PKCdelta was detected in all differentiated cell types, whereby PKCbetaII, gamma, epsilon, and zeta were solely found in the neuronal derivatives with PKCgamma predominantly located in the nuclei [29].
  • Moreover, this CCI-induced expression of NMDARs was significantly attenuated in rats receiving intrathecal treatment with an interleukin-6 (IL-6) antiserum and in mice with protein kinase Cgamma (PKCgamma) knock-out [30].
  • Events upstream of the NMDA receptor, especially the activation of the protein kinase Cgamma (PKCgamma), have been involved in the persistence of pain states associated with central sensitisation [31].
  • To reveal the functional differences of PKC subtypes, we examined the adaptability of ocular reflexes of PKCgamma mutant mice, which show mild ataxia and normal LTD [32].

Analytical, diagnostic and therapeutic context of Prkcc

  • This study identifies the PKCgamma as a key element that links opioid receptor activation with the recruitment of opposite systems to opioid analgesia involved in a physiological compensatory pain enhancement [31].
  • Acute stress has been shown to negatively affect hippocampal synaptic plasticity, and the present study examined the effect of acute stress on PKC gamma expression/subcellular distribution by quantitative western blotting in two inbred mouse strains (C57BL/6J versus DBA/2J) with established differences in hippocampal plasticity [33].
  • In further analysis by immunoblotting, this increased activity was found to be due to the increase in content of PKC gamma isozyme [34].
  • Immunoprecipitation with PKCgamma, but not with IgG antibody also yielded GABA(A) receptor alpha1 and alpha4 subunits in the immunoprecipitate [35].
  • Immunofluorescence double-labeling experiments conducted in the present study in naive and trained animals revealed that the principal cells and DG interneurons co-express mAChRs and PKC gamma, and that the immunoreactivity for both markers increased in relation to spatial orientation within these neurons [11].


  1. Alterations in protein kinase C isozymes alpha and beta 2 in activated Ha-ras containing papillomas in the absence of an increase in diacylglycerol. Mills, K.J., Bocckino, S.B., Burns, D.J., Loomis, C.R., Smart, R.C. Carcinogenesis (1992) [Pubmed]
  2. Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain. Gardell, L.R., Ibrahim, M., Wang, R., Wang, Z., Ossipov, M.H., Malan, T.P., Porreca, F., Lai, J. Neuroscience (2004) [Pubmed]
  3. The role of protein kinase C in the regulation of serotonin-2A receptor expression. Anji, A., Sullivan Hanley, N.R., Kumari, M., Hensler, J.G. J. Neurochem. (2001) [Pubmed]
  4. Differential staining of neurons in the human retina with antibodies to protein kinase C isozymes. Kolb, H., Zhang, L., Dekorver, L. Vis. Neurosci. (1993) [Pubmed]
  5. Protein kinase C gamma (PKC gamma): function of neuron specific isotype. Saito, N., Shirai, Y. J. Biochem. (2002) [Pubmed]
  6. Alterations of protein kinase C isozyme and substrate proteins in mouse brain after electroconvulsive seizures. Chen, C.C. Brain Res. (1994) [Pubmed]
  7. Changes in PKC gamma immunoreactivity in mouse hippocampus induced by spatial discrimination learning. Van der Zee, E.A., Compaan, J.C., de Boer, M., Luiten, P.G. J. Neurosci. (1992) [Pubmed]
  8. Impaired synapse elimination during cerebellar development in PKC gamma mutant mice. Kano, M., Hashimoto, K., Chen, C., Abeliovich, A., Aiba, A., Kurihara, H., Watanabe, M., Inoue, Y., Tonegawa, S. Cell (1995) [Pubmed]
  9. Modified hippocampal long-term potentiation in PKC gamma-mutant mice. Abeliovich, A., Chen, C., Goda, Y., Silva, A.J., Stevens, C.F., Tonegawa, S. Cell (1993) [Pubmed]
  10. Preserved acute pain and reduced neuropathic pain in mice lacking PKCgamma. Malmberg, A.B., Chen, C., Tonegawa, S., Basbaum, A.I. Science (1997) [Pubmed]
  11. Alterations in the immunoreactivity for muscarinic acetylcholine receptors and colocalized PKC gamma in mouse hippocampus induced by spatial discrimination learning. Van der Zee, E.A., Compaan, J.C., Bohus, B., Luiten, P.G. Hippocampus. (1995) [Pubmed]
  12. Differential sensitivity to the anxiolytic effects of ethanol and flunitrazepam in PKCgamma null mutant mice. Bowers, B.J., Elliott, K.J., Wehner, J.M. Pharmacol. Biochem. Behav. (2001) [Pubmed]
  13. Isolation and sequence of a mouse brain cDNA coding for protein kinase C-gamma isozyme. Bowers, B.J., Parham, C.L., Sikela, J.M., Wehner, J.M. Gene (1993) [Pubmed]
  14. Functional characterization of the promoter region of the mouse protein kinase C gamma gene. Takanaga, H., Mukai, H., Shimakawa, M., Konishi, H., Kikkawa, U., Koizumi, T., Ono, Y. FEBS Lett. (1995) [Pubmed]
  15. Influence of a deletion of protein kinase C gamma isoform in the G-protein activation mediated through opioid receptor-like-1 and mu-opioid receptors in the mouse pons/medulla. Narita, M., Mizoguchi, H., Khotib, J., Suzuki, M., Ozaki, S., Yajima, Y., Narita, M., Tseng, L.F., Suzuki, T. Neurosci. Lett. (2002) [Pubmed]
  16. Mice lacking PKC gamma exhibit decreased anxiety. Bowers, B.J., Collins, A.C., Tritto, T., Wehner, J.M. Behav. Genet. (2000) [Pubmed]
  17. Generation and characterization of the PKCgamma-Cre mouse line. Ding, Y.Q., Xiang, C.X., Chen, Z.F. Genesis (2005) [Pubmed]
  18. Altered trafficking of membrane proteins in purkinje cells of SCA1 transgenic mice. Skinner, P.J., Vierra-Green, C.A., Clark, H.B., Zoghbi, H.Y., Orr, H.T. Am. J. Pathol. (2001) [Pubmed]
  19. Regulation of spontaneous meiosis resumption in mouse oocytes by various conventional PKC isozymes depends on cellular compartmentalization. Avazeri, N., Courtot, A.M., Lefevre, B. J. Cell. Sci. (2004) [Pubmed]
  20. Loss of mouse epidermal protein kinase C isozyme activities following treatment with phorbol ester and non-phorbol ester tumor promoters. Wang, X.J., Warren, B.S., Rupp, T., Beltrán, L.M., DiGiovanni, J. Carcinogenesis (1994) [Pubmed]
  21. Mutant mice lacking the gamma isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of gamma-aminobutyrate type A receptors. Harris, R.A., McQuilkin, S.J., Paylor, R., Abeliovich, A., Tonegawa, S., Wehner, J.M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  22. Characterization of conventional protein kinase C (PKC) isotype expression during F9 teratocarcinoma differentiation. Overexpression of PKC alpha alters the expression of some differentiation-dependent genes. Kindregan, H.C., Rosenbaum, S.E., Ohno, S., Niles, R.M. J. Biol. Chem. (1994) [Pubmed]
  23. Reduced development of tolerance to the analgesic effects of morphine and clonidine in PKC gamma mutant mice. Zeitz, K.P., Malmberg, A.B., Gilbert, H., Basbaum, A.I. Pain (2001) [Pubmed]
  24. Protein kinase C is involved in clozapine's facilitation of N-methyl-D-aspartate- and electrically evoked responses in pyramidal cells of the medial prefrontal cortex. Jardemark, K.E., Ninan, I., Liang, X., Wang, R.Y. Neuroscience (2003) [Pubmed]
  25. Ethanol consumption and behavioral impulsivity are increased in protein kinase Cgamma null mutant mice. Bowers, B.J., Wehner, J.M. J. Neurosci. (2001) [Pubmed]
  26. Different regulation of Purkinje cell dendritic development in cerebellar slice cultures by protein kinase Calpha and -beta. Gundlfinger, A., Kapfhammer, J.P., Kruse, F., Leitges, M., Metzger, F. J. Neurobiol. (2003) [Pubmed]
  27. Immortalized mammary epithelial cells overexpressing protein kinase C gamma acquire a malignant phenotype and become tumorigenic in vivo. Mazzoni, E., Adam, A., Bal de Kier Joffe, E., Aguirre-Ghiso, J.A. Mol. Cancer Res. (2003) [Pubmed]
  28. Expression and activity of protein kinase C isoenzymes during normal and abnormal murine palate development. Balasubramanian, G., Amann, J.F., Reddy, C.S. J. Craniofac. Genet. Dev. Biol. (2000) [Pubmed]
  29. Expression of protein kinase C gene family members is temporally and spatially regulated during neural development in vitro. Oehrlein, S.A., Maelicke, A., Herget, T. Eur. J. Cell Biol. (1998) [Pubmed]
  30. Central glucocorticoid receptors modulate the expression and function of spinal NMDA receptors after peripheral nerve injury. Wang, S., Lim, G., Zeng, Q., Sung, B., Yang, L., Mao, J. J. Neurosci. (2005) [Pubmed]
  31. Prevention of fentanyl-induced delayed pronociceptive effects in mice lacking the protein kinase Cgamma gene. Célérier, E., Simonnet, G., Maldonado, R. Neuropharmacology (2004) [Pubmed]
  32. Role of protein kinase C family in the cerebellum-dependent adaptive learning of horizontal optokinetic response eye movements in mice. Shutoh, F., Katoh, A., Ohki, M., Itohara, S., Tonegawa, S., Nagao, S. Eur. J. Neurosci. (2003) [Pubmed]
  33. Acute restraint stress reduces protein kinase C gamma in the hippocampus of C57BL/6 but not DBA/2 mice. McNamara, R.K., Lenox, R.H. Neurosci. Lett. (2004) [Pubmed]
  34. Pentylenetetrazole-induced chemoshock affects protein kinase C and substrate proteins in mouse brain. Chen, C.C. J. Neurochem. (1994) [Pubmed]
  35. Association of protein kinase C with GABA(A) receptors containing alpha1 and alpha4 subunits in the cerebral cortex: selective effects of chronic ethanol consumption. Kumar, S., Sieghart, W., Morrow, A.L. J. Neurochem. (2002) [Pubmed]
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