Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2011, Vol. 5 Issue (1) : 70-76     DOI: 10.1007/s11684-011-0119-9
The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases
Yuan CHEN(), Qi TIAN
Neurobiology Research Center, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, China
Download: PDF(137 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Protein kinase C epsilon (PKC ?) is one of major isoforms in novel PKC family. Although it has been extensively characterized in the past decade, the role of PKC ? in neuron is still not well understood. Advances in molecular biology have now removed significant barriers to the direct investigation of PKC ? functions in vivo, and PKC ? has been increasingly implicated in the neural biological functions and associated neurogenic diseases. Recent studies have provided important insights into the influence of PKC ? on cortical processing at both the single cell level and network level. These studies provide compelling evidence that PKC ? could regulate distinct aspects of neural signal transduction and suggest that the coordinated actions of a number of molecular signals contribute to the specification and differentiation of PKC ? signal pathway in the developing brain.

Keywords protein kinase C ?      signal transduction      neurogenic disease     
Corresponding Authors: CHEN Yuan,   
Issue Date: 05 March 2011
URL:     OR
1 Battaini F. Protein kinase C isoforms as therapeutic targets in nervous system disease states. Pharmacol Res , 2001, 44(5): 353-361
doi: 10.1006/phrs.2001.0893 pmid:11712865
2 Chen G, Masana M I, Manji H K. Lithium regulates PKC-mediated intracellular cross-talk and gene expression in the CNS in vivo. Bipolar Disord , 2000, 2(3 Pt 2): 217-236
doi: 10.1034/j.1399-5618.2000.20303.x pmid:11249800
3 Nishizuka Y. Protein kinase C and lipid signaling for sustained cellular responses. FASEB J , 1995, 9(7): 484-496
4 Van Kolen K, Pullan S, Neefs J M, Dautzenberg F M. Nociceptive and behavioural sensitisation by protein kinase Cepsilon signalling in the CNS. J Neurochem , 2008, 104(1): 1-13
5 Bruch R C, Kang J S, Moore M L Jr, Medler K F. Protein kinase C and receptor kinase gene expression in olfactory receptor neurons. J Neurobiol , 1997, 33(4): 387-394
doi: 10.1002/(SICI)1097-4695(199710)33:4<387::AID-NEU4>3.0.CO;2-6 pmid:9322156
6 Zeidman R, L?fgren B, Pahlman S, Larsson C. PKCepsilon, via its regulatory domain and independently of its catalytic domain, induces neurite-like processes in neuroblastoma cells. J Cell Biol , 1999, 145(4): 713-726
doi: 10.1083/jcb.145.4.713 pmid:10330401
7 Patten S A, Sihra R K, Dhami K S, Coutts C A, Ali D W. Differential expression of PKC isoforms in developing zebrafish. Int J Dev Neurosci , 2007, 25(3): 155-164
doi: 10.1016/j.ijdevneu.2007.02.003 pmid:17403595
8 Shirai Y, Adachi N, Saito N. Protein kinase Cepsilon: function in neurons. FEBS J , 2008, 275(16): 3988-3994
doi: 10.1111/j.1742-4658.2008.06556.x pmid:18637121
9 Minami H, Owada Y, Suzuki R, Handa Y, Kondo H. Localization of mRNAs for novel, atypical as well as conventional protein kinase C (PKC) isoforms in the brain of developing and mature rats. J Mol Neurosci , 2000, 15(2): 121-135
doi: 10.1385/JMN:15:2:121 pmid:11220785
10 Saito N, Itouji A, Totani Y, Osawa I, Koide H, Fujisawa N, Ogita K, Tanaka C. Cellular and intracellular localization of epsilon-subspecies of protein kinase C in the rat brain; presynaptic localization of the epsilon-subspecies. Brain Res , 1993, 607(1-2): 241-248
doi: 10.1016/0006-8993(93)91512-Q pmid:8481800
11 Uhlén M, Bj?rling E, Agaton C, Szigyarto C A, Amini B, Andersen E, Andersson A C, Angelidou P, Asplund A, Asplund C, Berglund L, Bergstr?m K, Brumer H, Cerjan D, Ekstr?m M, Elobeid A, Eriksson C, Fagerberg L, Falk R, Fall J, Forsberg M, Bj?rklund M G, Gumbel K, Halimi A, Hallin I, Hamsten C, Hansson M, Hedhammar M, Hercules G, Kampf C, Larsson K, Lindskog M, Lodewyckx W, Lund J, Lundeberg J, Magnusson K, Malm E, Nilsson P, Odling J, Oksvold P, Olsson I, Oster E, Ottosson J, Paavilainen L, Persson A, Rimini R, Rockberg J, Runeson M, Sivertsson A, Sk?llermo A, Steen J, Stenvall M, Sterky F, Str?mberg S, Sundberg M, Tegel H, Tourle S, Wahlund E, Waldén A, Wan J, Wernérus H, Westberg J, Wester K, Wrethagen U, Xu L L, Hober S, Pontén F. A human protein atlas for normal and cancer tissues based on antibody proteomics. Mol Cell Proteomics , 2005, 4(12): 1920-1932
doi: 10.1074/mcp.M500279-MCP200 pmid:16127175
12 Uhlen M, Ponten F. Antibody-based proteomics for human tissue profiling. Mol Cell Proteomics , 2005, 4(4): 384-393
doi: 10.1074/mcp.R500009-MCP200 pmid:15695805
13 Akita Y. Protein kinase C-epsilon (PKC-epsilon): its unique structure and function. J Biochem , 2002, 132(6): 847-852
14 Yonezawa T, Kurata R, Kimura M, Inoko H. PKC delta and epsilon in drug targeting and therapeutics. Recent Pat DNA Gene Seq , 2009, 3(2): 96-101
doi: 10.2174/187221509788654205 pmid:19519579
15 Newton P M, Messing R O. The substrates and binding partners of protein kinase Cepsilon. Biochem J , 2010, 427(2): 189-196
doi: 10.1042/BJ20091302 pmid:20350291
16 Newton P M, Ron D. Protein kinase C and alcohol addiction. Pharmacol Res , 2007, 55(6): 570-577
doi: 10.1016/j.phrs.2007.04.008 pmid:17566760
17 Prekeris R, Mayhew M W, Cooper J B, Terrian D M. Identification and localization of an actin-binding motif that is unique to the epsilon isoform of protein kinase C and participates in the regulation of synaptic function. J Cell Biol , 1996, 132(1-2): 77-90
doi: 10.1083/jcb.132.1.77 pmid:8567732
18 Zeidman R, Trollér U, Raghunath A, P?hlman S, Larsson C. Protein kinase Cepsilon actin-binding site is important for neurite outgrowth during neuronal differentiation. Mol Biol Cell , 2002, 13(1): 12-24
doi: 10.1091/mbc.01-04-0210 pmid:11809819
19 Aksoy E, Goldman M, Willems F. Protein kinase C epsilon: a new target to control inflammation and immune-mediated disorders. Int J Biochem Cell Biol , 2004, 36(2): 183-188
doi: 10.1016/S1357-2725(03)00210-3 pmid:14643884
20 Basu A, Sivaprasad U. Protein kinase Cepsilon makes the life and death decision. Cell Signal , 2007, 19(8): 1633-1642
doi: 10.1016/j.cellsig.2007.04.008 pmid:17537614
21 Gorin M A, Pan Q. Protein kinase C epsilon: an oncogene and emerging tumor biomarker. Mol Cancer , 2009, 8(1): 9
doi: 10.1186/1476-4598-8-9 pmid:19228372
22 Zhu W G, Xu P, Cuascut F X, Hall A K, Oxford G S. Activin acutely sensitizes dorsal root ganglion neurons and induces hyperalgesia via PKC-mediated potentiation of transient receptor potential vanilloid I. J Neurosci , 2007, 27(50): 13770-13780
doi: 10.1523/JNEUROSCI.3822-07.2007 pmid:18077689
23 Keri G O L, Eros D. Signal transduction therapy with rationally designed kinase inhibitors. Curr Signal Transduct Ther , 2006, 1(1): 67-95
doi: 10.2174/157436206775269190
24 Johnson J A. Differential inhibition by alpha and epsilon PKC pseudosubstrate sequences: a putative mechanism for preferential PKC activation in neonatal cardiac myocytes. Life Sci , 2004, 74(25): 3153-3172
doi: 10.1016/j.lfs.2003.11.016 pmid:15081580
25 Hernandez A I, Blace N, Crary J F, Serrano P A, Leitges M, Libien J M, Weinstein G, Tcherapanov A, Sacktor T C. Protein kinase M zeta synthesis from a brain mRNA encoding an independent protein kinase C zeta catalytic domain. Implications for the molecular mechanism of memory. J Biol Chem , 2003, 278(41): 40305-40316 12857744
doi: 10.1074/jbc.M307065200
26 Saito N, Shirai Y. Protein kinase C gamma (PKC gamma): function of neuron specific isotype. J Biochem , 2002, 132(5): 683-687
27 Osten P, Hrabetova S, Sacktor T C. Differential downregulation of protein kinase C isoforms in spreading depression. Neurosci Lett , 1996, 221(1): 37-40
doi: 10.1016/S0304-3940(96)13280-8 pmid:9014175
28 Hussain R J, Carpenter D O. A comparison of the roles of protein kinase C in long-term potentiation in rat hippocampal areas CA1 and CA3. Cell Mol Neurobiol , 2005, 25(3-4): 649-661
doi: 10.1007/s10571-005-4045-8 pmid:16075383
29 Hussain R J, Carpenter D O. Development of synaptic responses and plasticity at the SC-CA1 and MF-CA3 synapses in rat hippocampus. Cell Mol Neurobiol , 2001, 21(4): 357-368
doi: 10.1023/A:1012602105208 pmid:11775066
30 Tao W Q, Xiao P, Xu S T, Hu X J, Ou Y Q. Changes of synaptic transmission efficiency in the MF-CA3 and PP-CA3 pathways of rat hippocampus during discrimination learning. Sheng Li Xue Bao , 1996, 48(5): 431-436
31 Hama H, Hara C, Yamaguchi K, Miyawaki A. PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes. Neuron , 2004, 41(3): 405-415
doi: 10.1016/S0896-6273(04)00007-8 pmid:14766179
32 Chen Y, Cantrell A R, Messing R O, Scheuer T, Catterall W A. Specific modulation of Na+ channels in hippocampal neurons by protein kinase C epsilon. J Neurosci , 2005, 25(2): 507-513
doi: 10.1523/JNEUROSCI.4089-04.2005 pmid:15647496
33 Villarreal C F, Sachs D, Funez M I, Parada C A, de Queiroz Cunha F, Ferreira S H. The peripheral pro-nociceptive state induced by repetitive inflammatory stimuli involves continuous activation of protein kinase A and protein kinase C epsilon and its Na(V)1.8 sodium channel functional regulation in the primary sensory neuron. Biochem Pharmacol , 2009, 77(5): 867-877
doi: 10.1016/j.bcp.2008.11.015 pmid:19073148
34 Squassina A, Congiu D, Manconi F, Manchia M, Chillotti C, Lampus S, Severino G, Zompo M D. The PDLIM5 gene and lithium prophylaxis: an association and gene expression analysis in Sardinian patients with bipolar disorder. Pharmacol Res , 2008, 57(5): 369-373
doi: 10.1016/j.phrs.2008.03.011 pmid:18456508
35 Chen Y, Lai M Z, Maeno-Hikichi Y, Zhang J F. Essential role of the LIM domain in the formation of the PKC epsilon-ENH-N-type Ca2+ channel complex. Cell Signal , 2006, 18(2): 215-224
doi: 10.1016/j.cellsig.2005.04.007 pmid:15979848
36 Zhang J, Chen Y, Lai M, and Maeno-Hikichi Y. A phosphatase is part of a PKC-n-type calcium channel signaling complex in neurons. Society for Neuroscience Abstract Viewer and Itinerary Planner, 2002, No. 115.7 .
37 Maeno-Hikichi Y, Chang S, Matsummura K, Lai M, Lin H, Nakagawa N, Kuroda S, Zhang J F. A PKC epsilon-ENH-channel complex spedifically modulates N-type Ca2+ channels. Nat Neurosci , 2003, 6(5): 468-475
38 Gardezi S R, Weber A M, Li Q, Wong F K, Stanley E F. PDLIM5 is not a neuronal CaV2.2 adaptor protein. Nat Neurosci , 2009, 12(8): 957-958 , author reply 958
doi: 10.1038/nn0809-957a pmid:19636345
39 Burgos M, Pastor M D, González J C, Martinez-Galan J R, Vaquero C F, Fradejas N, Benavides A, Hernández-Guijo J M, Tranque P, Calvo S. PKC epsilon upregulates voltage-dependent calcium channels in cultured astrocytes. Glia , 2007, 55(14): 1437-1448
doi: 10.1002/glia.20555 pmid:17676593
40 Saegusa H, Kurihara T, Zong S, Kazuno A, Matsuda Y, Nonaka T, Han W, Toriyama H, Tanabe T. Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J , 2001, 20(10): 2349-2356
doi: 10.1093/emboj/20.10.2349 pmid:11350923
41 Raval A P, Dave K R, DeFazio R A, Perez-Pinzon M A. epsilonPKC phosphorylates the mitochondrial K(+) (ATP) channel during induction of ischemic preconditioning in the rat hippocampus. Brain Res , 2007, 1184: 345-353
doi: 10.1016/j.brainres.2007.09.073 pmid:17988655
42 Song C Y, Xi H J, Yang L, Qu L H, Zi Y, Zhou J, Cui X G, Gao W, Wang N, Pan Z W, and Li W Z. Propofol inhibited the delayed rectifier potassium current (I(k)) via activation of protein kinase C epsilon in rat parietal cortical neurons. Eur J Pharmacol , 2011, 653(1–3): 16–20
43 Zeidman R, Pettersson L, Sailaja P R, Truedsson E, Fagerstr?m S, P?hlman S, Larsson C. Novel and classical protein kinase C isoforms have different functions in proliferation, survival and differentiation of neuroblastoma cells. Int J Cancer , 1999, 81(3): 494-501 10209967
doi: 10.1002/(SICI)1097-0215(19990505)81:3<494::AID-IJC26>3.0.CO;2-L
44 Kolkova K, Stensman H, Berezin V, Bock E, Larsson C. Distinct roles of PKC isoforms in NCAM-mediated neurite outgrowth. J Neurochem , 2005, 92(4): 886-894
doi: 10.1111/j.1471-4159.2004.02919.x pmid:15686491
45 Burry R W. PKC activators (phorbol ester or bryostatin) stimulate outgrowth of NGF-dependent neurites in a subline of PC12 cells. J Neurosci Res , 1998, 53(2): 214-222
doi: 10.1002/(SICI)1097-4547(19980715)53:2<214::AID-JNR10>3.0.CO;2-6 pmid:9671978
46 Mikule K, Sunpaweravong S, Gatlin J C, Pfenninger K H. Eicosanoid activation of protein kinase C epsilon: involvement in growth cone repellent signaling. J Biol Chem , 2003, 278(23): 21168-21177
doi: 10.1074/jbc.M211828200 pmid:12665507
47 Théodore L, Derossi D, Chassaing G, Llirbat B, Kubes M, Jordan P, Chneiweiss H, Godement P, Prochiantz A. Intraneuronal delivery of protein kinase C pseudosubstrate leads to growth cone collapse. J Neurosci , 1995, 15(11): 7158-7167
48 Isbister C M, O’Connor T P. Mechanisms of growth cone guidance and motility in the developing grasshopper embryo. J Neurobiol , 2000, 44(2): 271-280
doi: 10.1002/1097-4695(200008)44:2<271::AID-NEU15>3.0.CO;2-A pmid:10934328
49 Tessier-Lavigne M, Goodman C S. The molecular biology of axon guidance. Science , 1996, 274(5290): 1123-1133
doi: 10.1126/science.274.5290.1123 pmid:8895455
50 Ling M, Trollér U, Zeidman R, Lundberg C, Larsson C. Induction of neurites by the regulatory domains of PKC delta and epsilon is counteracted by PKC catalytic activity and by the RhoA pathway. Exp Cell Res , 2004, 292(1): 135-150
doi: 10.1016/j.yexcr.2003.08.013 pmid:14720513
51 Trollér U, Larsson C. Cdc42 is involved in PKCepsilon- and delta-induced neurite outgrowth and stress fibre dismantling. Biochem Biophys Res Commun , 2006, 349(1): 91-98
doi: 10.1016/j.bbrc.2006.07.200 pmid:16930532
52 Shirai Y, Murakami T, Kuramasu M, Iijima L, Saito N. A novel PIP2 binding of epsilon PKC and its contribution to the neurite induction ability. J Neurochem , 2007, 102(5): 1635-1644
doi: 10.1111/j.1471-4159.2007.04702.x pmid:17697049
53 Yamaguchi H, Shiraishi M, Fukami K, Tanabe A, Ikeda-Matsuo Y, Naito Y, Sasaki Y. MARCKS regulates lamellipodia formation induced by IGF-I via association with PIP2 and beta-actin at membrane microdomains. J Cell Physiol , 2009, 220(3): 748-755
doi: 10.1002/jcp.21822 pmid:19475567
54 Nguyen L, He Q, Meiri K F. Regulation of GAP-43 at serine 41 acts as a switch to modulate both intrinsic and extrinsic behaviors of growing neurons, via altered membrane distribution. Mol Cell Neurosci , 2009, 41(1): 62-73
doi: 10.1016/j.mcn.2009.01.011 pmid:19249369
55 Tauskela J S, chakravarthy B R, Murray C L, Wang Y Z, Comas T, Hogan M, Hakim A, Morley P. Evidence from cultured rat cortical neurons of differences in the mechanism of ischemic preconditioning of brain and heart. Brain Res , 1999, 827(1-2): 143-151
doi: 10.1016/S0006-8993(99)01322-0 pmid:10320703
56 Kim E J, Raval A P, Perez-Pinzon M A. Preconditioning mediated by sublethal oxygen-glucose deprivation-induced cyclooxygenase-2 expression via the signal transducers and activators of transcription 3 phosphorylation. J Cereb Blood Flow Metab , 2008, 28(7): 1329-1340
doi: 10.1038/jcbfm.2008.26 pmid:18398416
57 Wolfrum S, Schneider K, Heidbreder M, Nienstedt J, Dominiak P, Dendorfer A. Remote preconditioning protects the heart by activating myocardial PKCepsilon-isoform. Cardiovasc Res , 2002, 55(3): 583-589
doi: 10.1016/S0008-6363(02)00408-X pmid:12160956
58 Liu Z G, Xia Z Y, Chen X D, Luo T. Isoflurane induces expression of vascular endothelial growth factor through activating protein kinase C in myocardial cells. Chin J Traumatol , 2010, 13(5): 284-288
59 Budas G R, Mochly-Rosen D. Mitochondrial protein kinase Cepsilon (PKCepsilon): emerging role in cardiac protection from ischaemic damage. Biochem Soc Trans , 2007, 35(Pt 5): 1052-1054
doi: 10.1042/BST0351052 pmid:17956277
60 Dave K R, Anthony Defazio R, Raval A P, Dashkin O, Saul I, Iceman K E, Perez-Pinzon M A, Drew K L. Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel. J Neurochem , 2009, 110(4): 1170-1179
doi: 10.1111/j.1471-4159.2009.06196.x pmid:19493168
61 Ferreira J, Trichês K M, Medeiros R, Calixto J B. Mechanisms involved in the nociception produced by peripheral protein kinase c activation in mice. Pain , 2005, 117(1-2): 171-181
doi: 10.1016/j.pain.2005.06.001 pmid:16099101
62 Davis J B, Gray J, Gunthorpe M J, Hatcher J P, Davey P T, Overend P, Harries M H, Latcham J, Clapham C, Atkinson K, Hughes S A, Rance K, Grau E, Harper A J, Pugh P L, Rogers D C, Bingham S, Randall A, Sheardown S A. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature , 2000, 405(6783): 183-187
doi: 10.1038/35012076 pmid:10821274
63 Hucho T B, Dina O A, Kuhn J, Levine J D. Estrogen controls PKCepsilon-dependent mechanical hyperalgesia through direct action on nociceptive neurons. Eur J Neurosci , 2006, 24(2): 527-534
doi: 10.1111/j.1460-9568.2006.04913.x pmid:16836642
64 Sachs D, Villarreal C F, Cunha F Q, Parada C A, Ferreira Sh. The role of PKA and PKCepsilon pathways in prostaglandin E2-mediated hypernociception. Br J Pharmacol , 2009, 156(5): 826-834
doi: 10.1111/j.1476-5381.2008.00093.x pmid:19220288
65 Zhang H, Cang C L, Kawasaki Y, Liang L L, Zhang Y Q, Ji R R, Zhao Z Q. Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia. J Neurosci , 2007, 27(44): 12067-12077
doi: 10.1523/JNEUROSCI.0496-07.2007 pmid:17978048
66 Khasar S G, Lin Y H, Martin A, Dadgar J, McMahon T, Wang D, Hundle B, Aley K O, Isenberg W, McCarter G, Green P G, Hodge C W, Levine J D, Messing R O. A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice. Neuron , 1999, 24(1): 253-260
doi: 10.1016/S0896-6273(00)80837-5 pmid:10677042
67 Khasar S G, McCarter G, Levine J D. Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors. J Neurophysiol , 1999, 81(3): 1104-1112
68 Ferrari L F, Bogen O, Levine J D. Nociceptor subpopulations involved in hyperalgesic priming. Neuroscience , 2010, 165(3): 896-901
doi: 10.1016/j.neuroscience.2009.11.029 pmid:19931357
69 Amadesi S, Cottrell G S, Divino L, Chapman K, Grady E F, Bautista F, Karanjia R, Barajas-Lopez C, Vanner S, Vergnolle N, Bunnett N W. Protease-activated receptor 2 sensitizes TRPV1 by protein kinase C epsilon- and A-dependent mechanisms in rats and mice. J Physiol , 2006, 575(2): 555-571
doi: 10.1113/jphysiol.2006.111534
70 Bautista F, Amadesi S, Karanjia R, Barajas-Lopez C, Burnett N, Vanner S. Protease activated receptor 2 (PAR2) Sensitization of TRPV1 currents is mediated by protein kinase CE and protein kinase A. Gastroenterology , 2006, 130(4): A336-A336
71 Srinivasan R, Wolfe D, Goss J, Watkins S, de Groat W C, Sculptoreanu A, Glorioso J C. Protein kinase C epsilon contributes to basal and sensitizing responses of TRPV1 to capsaicin in rat dorsal root ganglion neurons. Eur J Neurosci , 2008, 28(7): 1241-1254
doi: 10.1111/j.1460-9568.2008.06438.x pmid:18973552
72 Sculptoreanu A, Aura Kullmann F, de Groat W C. Neurokinin 2 receptor-mediated activation of protein kinase C modulates capsaicin responses in DRG neurons from adult rats. Eur J Neurosci , 2008, 27(12): 3171-3181
doi: 10.1111/j.1460-9568.2008.06267.x pmid:18598261
73 Numazaki M, Tominaga T, Toyooka H, Tominaga M. Direct phosphorylation of capsaicin receptor VR1 by protein kinase Cepsilon and identification of two target serine residues. J Biol Chem , 2002, 277(16): 13375-13378
doi: 10.1074/jbc.C200104200 pmid:11884385
74 Mandadi S, Tominaga T, Numazaki M, Murayama N, Saito N, Armati P J, Roufogalis B D, Tominaga M. Tominaga, Numazaki M, Murayama N, Saito N, Armati P J, Roufogalis B D, and Tominaga M. Increased sensitivity of desensitized TRPV1 by PMA occurs through PKC epsilon-mediated phosphorylation at S800. Pain , 2006, 123(1-2): 106-116
doi: 10.1016/j.pain.2006.02.016 pmid:16564619
75 Honan S A, McNaughton P A. Sensitisation of TRPV1 in rat sensory neurones by activation of SNSRs. Neurosci Lett , 2007, 422(1): 1-6
doi: 10.1016/j.neulet.2007.04.083 pmid:17601667
76 Choi D S, Wang D, Chang W, McMahon T, Taylor S, Messing R O. Expression of the PKC epsilon in the brain controls ethanol-drinking behavior. Society for Neuroscience Abstracts , 2001, 27(1): 1495
77 Bajo M, Cruz M T, Siggins G R, Messing R, Roberto M. Protein kinase C epsilon mediation of CRF- and ethanol-induced GABA release in central amygdala. Proc Natl Acad Sci USA , 2008, 105(24): 8410-8415
doi: 10.1073/pnas.0802302105 pmid:18541912
78 Besheer J, Lepoutre V, Mole B, Hodge C W. GABAA receptor regulation of voluntary ethanol drinking requires PKCepsilon. Synapse , 2006, 60(6): 411-419
doi: 10.1002/syn.20314 pmid:16881070
79 Hodge C W, Raber J, McMahon T, Walter H, Sanchez-Perez A M, Olive M F, Mehmert K, Morrow A L, Messing R O. Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cepsilon. J Clin Invest , 2002, 110(7): 1003-1010
80 Hodge C W, Mehmert K K, Kelley S P, McMahon T, Haywood A, Olive M F, Wang D, Sanchez-Perez A M, Messing R O. Supersensitivity to allosteric GABA(A) receptor modulators and alcohol in mice lacking PKCepsilon. Nat Neurosci , 1999, 2(11): 997-1002
doi: 10.1038/14795 pmid:10526339
81 Das J, Pany S, Rahman G M, Slater S J. PKC epsilon has an alcohol-binding site in its second cysteine-rich regulatory domain. Biochem J , 2009, 421(3): 405-413
doi: 10.1042/BJ20082271 pmid:19432558
82 Jiang Z L, Ye J H. Protein kinase C epsilon is involved in ethanol potentiation of glycine-gated Cl(-) current in rat neurons of ventral tegmental area. Neuropharmacology , 2003, 44(4): 493-502
doi: 10.1016/S0028-3908(02)00409-4 pmid:12646286
83 Lesscher H M, Wallace M J, Zeng L, Wang V, Deitchman J K, McMahon T, Messing R O, Newton P M. Amygdala protein kinase C epsilon controls alcohol consumption. Genes Brain Behav , 2009, 8(5): 493-499
doi: 10.1111/j.1601-183X.2009.00485.x pmid:19243450
[1] Jiansong Huang,Yulan Zhou,Xiaoyu Su,Yuanjing Lyu,Lanlan Tao,Xiaofeng Shi,Ping Liu,Zhangbiao Long,Zheng Ruan,Bing Xiao,Wenda Xi,Quansheng Zhou,Jianhua Mao,Xiaodong Xi. Roles of integrin β3 cytoplasmic tail in bidirectional signal transduction in a trans-dominant inhibition model[J]. Front. Med., 2016, 10(3): 311-319.
[2] Feng Ye, Adam K. Snider, Mark H. Ginsberg. Talin and kindlin: the one-two punch in integrin activation[J]. Front Med, 2014, 8(1): 6-16.
[3] Ling XU MM, Feng WANG MM, Xuan-Fu XU MD, Wen-Hui MO BM, Rong WAN MD, Chuan-Yong GUO MD, Xing-Peng WANG MD, . Data mining of microarray for differentially expressed genes in liver metastasis from gastric cancer[J]. Front. Med., 2010, 4(2): 247-253.
[4] Wen YAN MD, Min FENG MD, Pei-Hua WANG MD, Dao-Wen WANG MD, . Effect of bradykinin on bradykinin-B2 receptor in rat aortic vascular smooth muscle cells and the involved signal transduction pathways[J]. Front. Med., 2010, 4(2): 225-228.
[5] Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD, . Mitogen-activated protein kinase pathway inhibitors: inhibitors for diseases?[J]. Front. Med., 2010, 4(1): 46-53.
[6] Rui ZHU MD , Lin SHEN MD , Jianguo LIU MD , Weili ZHANG MM , Ling YANG MD , . Effect of decoction on CD14 expression in lipopolysaccharide signal transduction pathway of alcohol-induced liver disease in rats[J]. Front. Med., 2009, 3(3): 363-367.
[7] GONG Xiaowei, WEI Jie, LI Yusheng, CHENG Weiwei, DENG Peng, JIANG Yong. Involvement of p38 mitogen-activated protein kinase in the regulation of platelet-derived growth factor -induced cell migration[J]. Front. Med., 2007, 1(3): 248-252.
Full text