1tbo

Structural highlights

Function

KPCG_RAT 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 contributes 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. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity).[UniProtKB:P63318]^{[1] [2] [3] [4] [5] [6]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Protein kinase C 3D structures

References

1. ↑ Martin WJ, Liu H, Wang H, Malmberg AB, Basbaum AI. Inflammation-induced up-regulation of protein kinase Cgamma immunoreactivity in rat spinal cord correlates with enhanced nociceptive processing. Neuroscience. 1999;88(4):1267-74. PMID:10336135 doi:10.1016/s0306-4522(98)00314-5
2. ↑ Correia SS, Duarte CB, Faro CJ, Pires EV, Carvalho AL. Protein kinase C gamma associates directly with the GluR4 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit. Effect on receptor phosphorylation. J Biol Chem. 2003 Feb 21;278(8):6307-13. PMID:12471040 doi:10.1074/jbc.M205587200
3. ↑ Hamabe W, Fujita R, Ueda H. Insulin receptor-protein kinase C-gamma signaling mediates inhibition of hypoxia-induced necrosis of cortical neurons. J Pharmacol Exp Ther. 2005 Jun;313(3):1027-34. PMID:15705736 doi:10.1124/jpet.104.082735
4. ↑ Sánchez-Pérez AM, Felipo V. Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms. Neurochem Int. 2005 Jul;47(1-2):84-91. PMID:15936117 doi:10.1016/j.neuint.2005.04.011
5. ↑ 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
6. ↑ Krugers HJ, Douma BR, Andringa G, Bohus B, Korf J, Luiten PG. Exposure to chronic psychosocial stress and corticosterone in the rat: effects on spatial discrimination learning and hippocampal protein kinase Cgamma immunoreactivity. Hippocampus. 1997;7(4):427-36. PMID:9287082 doi:<427::AID-HIPO8>3.0.CO;2-F 10.1002/(SICI)1098-1063(1997)7:4<427::AID-HIPO8>3.0.CO;2-F
7. ↑ 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