| Structural highlights
Function
[KPCG_MOUSE] Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contribute to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress. Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage (By similarity).[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Classical protein kinase C (PKC) family members are activated by the binding of various ligands to one of several cysteine-rich domains of the enzyme. The natural agonist, diacylglycerol (DAG), and the natural product superagonist, phorbol dibutyrate (PDB), activate the enzyme to produce wide-ranging physiological effects. The second cysteine-rich (Cys2) domain of rat brain PKC-gamma was expressed and labeled with 15N and 13C, and the solution structure was determined to high resolution using multidimensional heteronuclear NMR methods. The phorbol binding site was identified by titrating this domain with phorbol-12,13-dibutyrate (PDB) in the presence of organic cosolvents. Titrations of this domain with lipid micelles, in the absence and presence of phorbols, indicate selective broadening of some resonances. The observed behavior indicates conformational exchange between bound and free states upon protein-micelle interaction. The data also suggest that half of the domain, including the phorbol site and one of the zinc sites, is capable of inserting into membranes.
NMR structure of a protein kinase C-gamma phorbol-binding domain and study of protein-lipid micelle interactions.,Xu RX, Pawelczyk T, Xia TH, Brown SC Biochemistry. 1997 Sep 2;36(35):10709-17. PMID:9271501[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Abeliovich A, Chen C, Goda Y, Silva AJ, Stevens CF, Tonegawa S. Modified hippocampal long-term potentiation in PKC gamma-mutant mice. Cell. 1993 Dec 31;75(7):1253-62. PMID:8269509
- ↑ Malmberg AB, Chen C, Tonegawa S, Basbaum AI. Preserved acute pain and reduced neuropathic pain in mice lacking PKCgamma. Science. 1997 Oct 10;278(5336):279-83. PMID:9323205
- ↑ Narita M, Mizoguchi H, Suzuki T, Narita M, Dun NJ, Imai S, Yajima Y, Nagase H, Suzuki T, Tseng LF. Enhanced mu-opioid responses in the spinal cord of mice lacking protein kinase Cgamma isoform. J Biol Chem. 2001 May 4;276(18):15409-14. Epub 2001 Jan 29. PMID:11278552 doi:http://dx.doi.org/10.1074/jbc.M009716200
- ↑ Narita M, Mizoguchi H, Narita M, Nagase H, Suzuki T, Tseng LF. Involvement of spinal protein kinase Cgamma in the attenuation of opioid mu-receptor-mediated G-protein activation after chronic intrathecal administration of [D-Ala2,N-MePhe4,Gly-Ol(5)]enkephalin. J Neurosci. 2001 Jun 1;21(11):3715-20. PMID:11356858
- ↑ Narita M, Aoki T, Ozaki S, Yajima Y, Suzuki T. Involvement of protein kinase Cgamma isoform in morphine-induced reinforcing effects. Neuroscience. 2001;103(2):309-14. PMID:11246146
- ↑ Zeitz KP, Malmberg AB, Gilbert H, Basbaum AI. Reduced development of tolerance to the analgesic effects of morphine and clonidine in PKC gamma mutant mice. Pain. 2001 Dec;94(3):245-53. PMID:11731061
- ↑ Ikeda A, Miyazaki T, Kakizawa S, Okuno Y, Tsuchiya S, Myomoto A, Saito SY, Yamamoto T, Yamazaki T, Iino M, Tsujimoto G, Watanabe M, Takeshima H. Abnormal features in mutant cerebellar Purkinje cells lacking junctophilins. Biochem Biophys Res Commun. 2007 Nov 23;363(3):835-9. Epub 2007 Sep 24. PMID:17904530 doi:http://dx.doi.org/10.1016/j.bbrc.2007.09.062
- ↑ Xu RX, Pawelczyk T, Xia TH, Brown SC. NMR structure of a protein kinase C-gamma phorbol-binding domain and study of protein-lipid micelle interactions. Biochemistry. 1997 Sep 2;36(35):10709-17. PMID:9271501 doi:10.1021/bi970833a
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