[en] Acute or chronic injury to the central nervous system (CNS), causes neuronal death and irreversible cognitive deficits or sensory-motor alteration. Despite the capacity of the adult CNS to generate new neurons from neural stem cells (NSC), neuronal replacement following an injury is a restricted process, which does not naturally result in functional regeneration. Therefore, potentiating endogenous neurogenesis is one of the strategies that are currently being under study to regenerate damaged brain tissue. The insignificant neurogenesis that occurs in CNS injuries is a consequence of the gliogenic/non-neurogenic environment that inflammatory signaling molecules create within the injured area. The modification of the extracellular signals to generate a neurogenic environment would facilitate neuronal replacement. However, in order to generate this environment, it is necessary to unearth which molecules promote or impair neurogenesis to introduce the first and/or eliminate the latter. Specific isozymes of the protein kinase C (PKC) family differentially contribute to generate a gliogenic or neurogenic environment in injuries by regulating the ADAM17 mediated release of growth factor receptor ligands. Recent reports describe several non-tumorigenic diterpenes isolated from plants of the Euphorbia genus, which specifically modulate the activity of PKC isozymes promoting neurogenesis. Diterpenes with 12-deoxyphorbol or lathyrane skeleton, increase NPC proliferation in neurogenic niches in the adult mouse brain in a PKCβ dependent manner exerting their effects on transit amplifying cells, whereas PKC inhibition in injuries promotes neurogenesis. Thus, compounds that balance PKC activity in injuries might be of use in the development of new drugs and therapeutic strategies to regenerate brain injuries.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology Life sciences: Multidisciplinary, general & others
Author, co-author :
Geribaldi-Doldán, Noelia; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomedica de Cádiz (INIBICA), Cádiz, Spain
Gómez Oliva, Ricardo ; Université de Liège - ULiège > GIGA > GIGA Neurosciences - Molecular Regulation of Neurogenesis ; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomedica de Cádiz (INIBICA), Cádiz, Spain
Domínguez-García, Samuel; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomedica de Cádiz (INIBICA), Cádiz, Spain
Nunez-Abades, Pedro; Instituto de Investigación e Innovación Biomedica de Cádiz (INIBICA), Cádiz, Spain ; Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Seville, Spain
Castro, Carmen; Área de Fisiología, Facultad de Medicina, Universidad de Cádiz, Cádiz, Spain ; Instituto de Investigación e Innovación Biomedica de Cádiz (INIBICA), Cádiz, Spain
Language :
English
Title :
Protein Kinase C: Targets to Regenerate Brain Injuries?
Alfonso, S. I., Callender, J. A., Hooli, B., Antal, C. E., Mullin, K., Sherman, M. A., et al. (2016). Gain-of-function mutations in protein kinase Calpha (PKCalpha) may promote synaptic defects in Alzheimer's disease. Sci. Signal. 9:ra47. doi: 10.1126/scisignal.aaf6209
Anton, E. S., Ghashghaei, H. T., Weber, J. L., Mccann, C., Fischer, T. M., Cheung, I. D., et al. (2004). Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain. Nat. Neurosci. 7, 1319-1328. doi: 10.1038/nn1345
Arvidsson, A., Collin, T., Kirik, D., Kokaia, Z., and Lindvall, O. (2002). Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat. Med. 8, 963-970. doi: 10.1038/nm747
Baldwin, R. M., Parolin, D. A., and Lorimer, I. A. (2008). Regulation of glioblastoma cell invasion by PKC iota and RhoB. Oncogene 27, 3587-3595. doi: 10.1038/sj.onc.1211027
Barker, R. A., Gotz, M., and Parmar, M. (2018). New approaches for brain repair-from rescue to reprogramming. Nature 557, 329-334. doi: 10.1038/s41586-018-0087-1
Basu, A., and Pal, D. (2010). Two faces of protein kinase Cdelta: the contrasting roles of PKCdelta in cell survival and cell death. ScientificWorldJournal 10, 2272-2284. doi: 10.1100/tsw.2010.214
Baxter, G., Oto, E., Daniel-Issakani, S., and Strulovici, B. (1992). Constitutive presence of a catalytic fragment of protein kinase C epsilon in a small cell lung carcinoma cell line. J. Biol. Chem. 267, 1910-1917
Benner, E. J., Luciano, D., Jo, R., Abdi, K., Paez-Gonzalez, P., Sheng, H., et al. (2013). Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4. Nature 497, 369-373. doi: 10.1038/nature12069
Black, A. R., and Black, J. D. (2012). Protein kinase C signaling and cell cycle regulation. Front. Immunol. 3:423. doi: 10.3389/fimmu.2012.00423
Blennow, K., Hardy, J., and Zetterberg, H. (2012). The neuropathology and neurobiology of traumatic brain injury. Neuron 76, 886-899. doi: 10.1016/j.neuron.2012.11.021
Blobel, C. P. (2005). ADAMs: key components in EGFR signalling and development. Nat. Rev. Mol. Cell. Biol. 6, 32-43. doi: 10.1038/nrm1548
Bogard, A. S., and Tavalin, S. J. (2015). Protein kinase C (PKC)zeta pseudosubstrate inhibitor peptide promiscuously binds PKC family isoforms and disrupts conventional PKC targeting and translocation. Mol. Pharmacol. 88, 728-735. doi: 10.1124/mol.115.099457
Braun, D. C., Cao, Y., Wang, S., Garfield, S. H., Min Hur, G., and Blumberg, P. M. (2005). Role of phorbol ester localization in determining protein kinase C or RasGRP3 translocation: real-time analysis using fluorescent ligands and proteins. Mol. Cancer Ther. 4, 141-150
Buffo, A., Rite, I., Tripathi, P., Lepier, A., Colak, D., Horn, A. P., et al. (2008). Origin and progeny of reactive gliosis: a source of multipotent cells in the injured brain. Proc. Natl. Acad. Sci. U.S.A. 105, 3581-3586. doi: 10.1073/pnas.0709002105
Cabodi, S., Calautti, E., Talora, C., Kuroki, T., Stein, P. L., and Dotto, G. P. (2000). A PKC-eta/Fyn-dependent pathway leading to keratinocyte growth arrest and differentiation. Mol. Cell 6, 1121-1129. doi: 10.1016/S1097-2765(00)00110-6
Chen, J., Magavi, S. S., and Macklis, J. D. (2004). Neurogenesis of corticospinal motor neurons extending spinal projections in adult mice. Proc. Natl. Acad. Sci. U.S.A. 101, 16357-16362. doi: 10.1073/pnas.0406795101
Codega, P., Silva-Vargas, V., Paul, A., Maldonado-Soto, A. R., Deleo, A. M., Pastrana, E., et al. (2014). Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron 82, 545-559. doi: 10.1016/j.neuron.2014.02.039
Corbit, K. C., Soh, J. W., Yoshida, K., Eves, E. M., Weinstein, I. B., and Rosner, M. R. (2000). Different protein kinase C isoforms determine growth factor specificity in neuronal cells. Mol. Cell. Biol. 20, 5392-5403. doi: 10.1128/MCB.20.15.5392-5403.2000
Dang, M., Armbruster, N., Miller, M. A., Cermeno, E., Hartmann, M., Bell, G. W., et al. (2013). Regulated ADAM17-dependent EGF family ligand release by substrate-selecting signaling pathways. Proc. Natl. Acad. Sci. U.S.A. 110, 9776-9781. doi: 10.1073/pnas.1307478110
Dang, M., Dubbin, K., D'aiello, A., Hartmann, M., Lodish, H., and Herrlich, A. (2011). Epidermal growth factor (EGF) ligand release by substrate-specific a disintegrin and metalloproteases (ADAMs) involves different protein kinase C (PKC) isoenzymes depending on the stimulus. J. Biol. Chem. 286, 17704-17713. doi: 10.1074/jbc.M110.187823
Deleers, M., and Malaisse, W. J. (1982). Binding of tumor-promoting and biologically inactive phorbol esters to artificial membranes. Cancer Lett. 17, 135-140. doi: 10.1016/0304-3835(82)90025-8
Dempsey, E. C., Newton, A. C., Mochly-Rosen, D., Fields, A. P., Reyland, M. E., Insel, P. A., et al. (2000). Protein kinase C isozymes and the regulation of diverse cell responses. Am. J. Physiol. Lung Cell. Mol. Physiol. 279, L429-L438. doi: 10.1152/ajplung.2000.279.3.L429
Doetsch, F., Caille, I., Lim, D. A., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (1999). Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703-716. doi: 10.1016/S0092-8674(00)80783-7
Doetsch, F., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (1997). Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J. Neurosci. 17, 5046-5061. doi: 10.1523/JNEUROSCI.17-13-05046.1997
Doetsch, F., Petreanu, L., Caille, I., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (2002). EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36, 1021-1034. doi: 10.1016/S0896-6273(02)01133-9
Du, Y., Zhao, Y., Li, C., Zheng, Q., Tian, J., Li, Z., et al. (2018). Inhibition of PKCdelta reduces amyloid-beta levels and reverses Alzheimer disease phenotypes. J. Exp. Med. 215, 1665-1677. doi: 10.1084/jem.20171193
Einat, H., Yuan, P., Szabo, S. T., Dogra, S., and Manji, H. K. (2007). Protein kinase C inhibition by tamoxifen antagonizes manic-like behavior in rats: implications for the development of novel therapeutics for bipolar disorder. Neuropsychobiology 55, 123-131. doi: 10.1159/000106054
Fallon, J., Reid, S., Kinyamu, R., Opole, I., Opole, R., Baratta, J., et al. (2000). In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain. Proc. Natl. Acad. Sci. U.S.A. 97, 14686-14691. doi: 10.1073/pnas.97.26.14686
Fatope, M. O., Zeng, L., Ohayaga, J. E., Shi, G., and Mclaughlin, J. L. (1996). Selectively cytotoxic diterpenes from Euphorbia poisonii. J. Med. Chem. 39, 1005-1008. doi: 10.1021/jm950509i
García-Bernal, F., Geribaldi-Doldán, N., Domínguez-García, S., Carrasco, M., Murillo-Carretero, M., Delgado-Ariza, A., et al. (2018). Protein kinase C inhibition mediates neuroblast enrichment in mechanical brain injuries. Front. Cell. Neurosci. 12:462. doi: 10.3389/fncel.2018.00462
Geraldes, P., and King, G. L. (2010). Activation of protein kinase C isoforms and its impact on diabetic complications. Circ. Res. 106, 1319-1331. doi: 10.1161/CIRCRESAHA.110.217117
Geribaldi-Doldan, N., Carrasco, M., Murillo-Carretero, M., Dominguez-Garcia, S., Garcia-Cozar, F. J., Munoz-Miranda, J. P., et al. (2018). Specific inhibition of ADAM17/TACE promotes neurogenesis in the injured motor cortex. Cell Death Dis. 9:862. doi: 10.1038/s41419-018-0913-2
Geribaldi-Doldan, N., Flores-Giubi, E., Murillo-Carretero, M., Garcia-Bernal, F., Carrasco, M., Macias-Sanchez, A. J., et al. (2016). 12-deoxyphorbols promote adult neurogenesis by inducing neural progenitor cell proliferation via PKC activation. Int. J. Neuropsychopharmacol. 19:yv085. doi: 10.1093/ijnp/pyv085
Ghashghaei, H. T., Weber, J., Pevny, L., Schmid, R., Schwab, M. H., Lloyd, K. C., et al. (2006). The role of neuregulin-ErbB4 interactions on the proliferation and organization of cells in the subventricular zone. Proc. Natl. Acad. Sci. U.S.A. 103, 1930-1935. doi: 10.1073/pnas.0510410103
Gonzalez-Perez, O., Romero-Rodriguez, R., Soriano-Navarro, M., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (2009). Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes. Stem Cells 27, 2032-2043. doi: 10.1002/stem.119
Gouveia, A., Hsu, K., Niibori, Y., Seegobin, M., Cancino, G. I., He, L., et al. (2016). The aPKC-CBP pathway regulates adult hippocampal neurogenesis in an age-dependent manner. Stem Cell Rep. 7, 719-734. doi: 10.1016/j.stemcr.2016.08.007
Grade, S., and Gotz, M. (2017). Neuronal replacement therapy: previous achievements and challenges ahead. NPJ Regen. Med. 2:29. doi: 10.1038/s41536-017-0033-0
Guo, J., Zhu, T., Luo, L. Y., Huang, Y., Sunkavalli, R. G., and Chen, C. Y. (2009). PI3K Acts in synergy with loss of PKC to elicit apoptosis via the UPR. J. Cell Biochem. 107, 76-85. doi: 10.1002/jcb.22102
Hansra, G., Garcia-Paramio, P., Prevostel, C., Whelan, R. D., Bornancin, F., and Parker, P. J. (1999). Multisite dephosphorylation and desensitization of conventional protein kinase C isotypes. Biochem. J. 342(Pt 2), 337-344. doi: 10.1042/bj3420337
Huang, S., Ouyang, N., Lin, L., Chen, L., Wu, W., Su, F., et al. (2012). HGF-induced PKCzeta activation increases functional CXCR4 expression in human breast cancer cells. PLoS One 7:e29124. doi: 10.1371/journal.pone.0029124
Inagaki, K., Churchill, E., and Mochly-Rosen, D. (2006). Epsilon protein kinase C as a potential therapeutic target for the ischemic heart. Cardiovasc. Res. 70, 222-230. doi: 10.1016/j.cardiores.2006.02.015
Jin, K., Minami, M., Lan, J. Q., Mao, X. O., Batteur, S., Simon, R. P., et al. (2001). Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc. Natl. Acad. Sci. U.S.A. 98, 4710-4715. doi: 10.1073/pnas.081011098
Kandasamy, M., Rosskopf, M., Wagner, K., Klein, B., Couillard-Despres, S., Reitsamer, H. A., et al. (2015). Reduction in subventricular zone-derived olfactory bulb neurogenesis in a rat model of Huntington's disease is accompanied by striatal invasion of neuroblasts. PLoS One 10:e0116069. doi: 10.1371/journal.pone.0116069
Kirby, J., Nishimoto, M., Park, J. G., Withers, S. T., Nowroozi, F., Behrendt, D., et al. (2010). Cloning of casbene and neocembrene synthases from Euphorbiaceae plants and expression in Saccharomyces cerevisiae. Phytochemistry 71, 1466-1473. doi: 10.1016/j.phytochem.2010.06.001
Konopatskaya, O., and Poole, A. W. (2010). Protein kinase Calpha: disease regulator and therapeutic target. Trends Pharmacol. Sci. 31, 8-14. doi: 10.1016/j.tips.2009.10.006
Kraft, A. S., Anderson, W. B., Cooper, H. L., and Sando, J. J. (1982). Decrease in cytosolic calcium/phospholipid-dependent protein kinase activity following phorbol ester treatment of EL4 thymoma cells. J. Biol. Chem. 257, 13193-13196
Kuhn, H. G., Dickinson-Anson, H., and Gage, F. H. (1996). Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J. Neurosci. 16, 2027-2033. doi: 10.1523/JNEUROSCI.16-06-02027.1996
Kuhn, H. G., Winkler, J., Kempermann, G., Thal, L. J., and Gage, F. H. (1997). Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J. Neurosci. 17, 5820-5829. doi: 10.1523/JNEUROSCI.17-15-05820.1997
Lee, D. C., Sunnarborg, S. W., Hinkle, C. L., Myers, T. J., Stevenson, M. Y., Russell, W. E., et al. (2003). TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase. Ann. N. Y. Acad. Sci. 995, 22-38. doi: 10.1111/j.1749-6632.2003.tb03207.x
Lesyk, G., Fong, T., Ruvolo, P. P., and Jurasz, P. (2015). The potential of enzastaurin to enhance platelet aggregation and growth factor secretion: implications for cancer cell survival. J. Thromb. Haemost. 13, 1514-1520. doi: 10.1111/jth.13010
Lim, D. A., Tramontin, A. D., Trevejo, J. M., Herrera, D. G., Garcia-Verdugo, J. M., and Alvarez-Buylla, A. (2000). Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713-726. doi: 10.1016/S0896-6273(00)00148-3
Liu, C., Peng, Z., Zhang, N., Yu, L., Han, S., Li, D., et al. (2012). Identification of differentially expressed microRNAs and their PKC-isoform specific gene network prediction during hypoxic pre-conditioning and focal cerebral ischemia of mice. J. Neurochem. 120, 830-841. doi: 10.1111/j.1471-4159.2011.07624.x
Liu, J., Solway, K., Messing, R. O., and Sharp, F. R. (1998). Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J. Neurosci. 18, 7768-7778. doi: 10.1523/JNEUROSCI.18-19-07768.1998
Liu, Q., and Molkentin, J. D. (2011). Protein kinase Calpha as a heart failure therapeutic target. J. Mol. Cell. Cardiol. 51, 474-478. doi: 10.1016/j.yjmcc.2010.10.004
Lucke-Wold, B. P., Turner, R. C., Logsdon, A. F., Simpkins, J. W., Alkon, D. L., Smith, K. E., et al. (2015). Common mechanisms of Alzheimer's disease and ischemic stroke: the role of protein kinase C in the progression of age-related neurodegeneration. J. Alzheimers Dis. 43, 711-724. doi: 10.3233/JAD-141422
Luzzati, F., Nato, G., Oboti, L., Vigna, E., Rolando, C., Armentano, M., et al. (2014). Quiescent neuronal progenitors are activated in the juvenile guinea pig lateral striatum and give rise to transient neurons. Development 141, 4065-4075. doi: 10.1242/dev.107987
Ma, W., Baumann, C., and Viveiros, M. M. (2015). Lack of protein kinase C-delta (PKCdelta) disrupts fertilization and embryonic development. Mol. Reprod. Dev. 82, 797-808. doi: 10.1002/mrd.22528
Magavi, S. S., Leavitt, B. R., and Macklis, J. D. (2000). Induction of neurogenesis in the neocortex of adult mice. Nature 405, 951-955. doi: 10.1038/35016083
Malla, R. R., Gopinath, S., Alapati, K., Gorantla, B., Gondi, C. S., and Rao, J. S. (2012). uPAR and cathepsin B inhibition enhanced radiation-induced apoptosis in gliomainitiating cells. Neuro Oncol. 14, 745-760. doi: 10.1093/neuonc/nos088
Márquez, N., Calzado, M. A., Sánchez-Duffhues, G., Pérez, M., Minassi, A., Pagani, A., et al. (2008). Differential effects of phorbol-13-monoesters on human immunodeficiency virus reactivation. Biochem. Pharmacol. 75, 1370-1380. doi: 10.1016/j.bcp.2007.12.004
Mellor, H., and Parker, P. J. (1998). The extended protein kinase C superfamily. Biochem. J. 332(Pt 2), 281-292. doi: 10.1042/bj3320281
Minami, H., Owada, Y., Suzuki, R., Handa, Y., and Kondo, H. (2000). 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. 15, 121-135. doi: 10.1385/JMN:15:2:121
Murillo-Carretero, M., Geribaldi-Doldan, N., Flores-Giubi, E., Garcia-Bernal, F., Navarro-Quiroz, E. A., Carrasco, M., et al. (2017). ELAC (3, 12-di-O-acetyl-8-O-tigloilingol), a plant-derived lathyrane diterpene, induces subventricular zone neural progenitor cell proliferation through PKCbeta activation. Br. J. Pharmacol. 174, 2373-2392. doi: 10.1111/bph.13846
Murphy, T. V., Prountzos, C., Kotsonis, P., Iannazzo, L., and Majewski, H. (1999). Structural determinants of phorbol ester binding in synaptosomes: pharmacokinetics and pharmacodynamics. Eur. J. Pharmacol. 381, 77-84. doi: 10.1016/S0014-2999(99)00540-3
Newton, A. C. (1995). Protein kinase C: seeing two domains. Curr. Biol. 5, 973-976. doi: 10.1016/S0960-9822(95)00191-6
Newton, A. C. (2018a). Protein kinase C as a tumor suppressor. Semin. Cancer Biol. 48, 18-26. doi: 10.1016/j.semcancer.2017.04.017
Newton, A. C. (2018b). Protein kinase C: perfectly balanced. Crit. Rev. Biochem. Mol. Biol. 53, 208-230. doi: 10.1080/10409238.2018.1442408
Ou, W. B., Zhu, M. J., Demetri, G. D., Fletcher, C. D., and Fletcher, J. A. (2008). Protein kinase C-theta regulates KIT expression and proliferation in gastrointestinal stromal tumors. Oncogene 27, 5624-5634. doi: 10.1038/onc.2008.177
Parent, J. M., Yu, T. W., Leibowitz, R. T., Geschwind, D. H., Sloviter, R. S., and Lowenstein, D. H. (1997). Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J. Neurosci. 17, 3727-3738. doi: 10.1523/JNEUROSCI.17-10-03727.1997
Pascale, A., Amadio, M., Govoni, S., and Battaini, F. (2007). The aging brain, a key target for the future: the protein kinase C involvement. Pharmacol. Res. 55, 560-569. doi: 10.1016/j.phrs.2007.04.013
Puls, A., Schmidt, S., Grawe, F., and Stabel, S. (1997). Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein. Proc. Natl. Acad. Sci. U.S.A. 94, 6191-6196. doi: 10.1073/pnas.94.12.6191
Reyland, M. E. (2009). Protein kinase C isoforms: multi-functional regulators of cell life and death. Front. Biosci. 14:2386-2399. doi: 10.2741/3385
Reynolds, B. A., and Weiss, S. (1992). Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707-1710. doi: 10.1126/science.1553558
Romero-Grimaldi, C., Murillo-Carretero, M., Lopez-Toledano, M. A., Carrasco, M., Castro, C., and Estrada, C. (2011). ADAM-17/tumor necrosis factor-alpha-converting enzyme inhibits neurogenesis and promotes gliogenesis from neural stem cells. Stem Cells 29, 1628-1639. doi: 10.1002/stem.710
Rosse, C., Linch, M., Kermorgant, S., Cameron, A. J., Boeckeler, K., and Parker, P. J. (2010). PKC and the control of localized signal dynamics. Nat. Rev. Mol. Cell. Biol. 11, 103-112. doi: 10.1038/nrm2847
Saha, B., Jaber, M., and Gaillard, A. (2012). Potentials of endogenous neural stem cells in cortical repair. Front. Cell. Neurosci. 6:14. doi: 10.3389/fncel.2012.00014
Saito, N., and Shirai, Y. (2002). Protein kinase C gamma (PKC gamma): function of neuron specific isotype. J. Biochem. 132, 683-687. doi: 10.1093/oxfordjournals.jbchem.a003274
Schmidt, R. J., and Evans, F. J. (1977). Succulent euphorbias of nigeria.2. Aliphatic diterpene esters of lattices of euphorbia-poisonii pax and euphorbia-unispina Ne Br. Lloydia 40, 225-229
Singh, R. K., Kumar, S., Gautam, P. K., Tomar, M. S., Verma, P. K., Singh, S. P., et al. (2017). Protein kinase C-alpha and the regulation of diverse cell responses. Biomol. Concepts 8, 143-153. doi: 10.1515/bmc-2017-0005
Sledge, G. W. Jr., and Gokmen-Polar, Y. (2006). Protein kinase C-beta as a therapeutic target in breast cancer. Semin. Oncol. 33, S15-S18
Steinhart, R., Kazimirsky, G., Okhrimenko, H., Ben-Hur, T., and Brodie, C. (2007). PKCepsilon induces astrocytic differentiation of multipotential neural precursor cells. Glia 55, 224-232. doi: 10.1002/glia.20454
Sun, M. K., and Alkon, D. L. (2014). The "memory kinases": roles of PKC isoforms in signal processing and memory formation. Prog. Mol. Biol. Transl. Sci. 122, 31-59. doi: 10.1016/B978-0-12-420170-5.00002-7
Sunnarborg, S. W., Hinkle, C. L., Stevenson, M., Russell, W. E., Raska, C. S., Peschon, J. J., et al. (2002). Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. J. Biol. Chem. 277, 12838-12845. doi: 10.1074/jbc.M112050200
Susarla, B. T., Villapol, S., Yi, J. H., Geller, H. M., and Symes, A. J. (2014). Temporal patterns of cortical proliferation of glial cell populations after traumatic brain injury in mice. ASN Neuro 6, 159-170. doi: 10.1042/AN20130034
Sweitzer, S. M., Wong, S. M., Tjolsen, A., Allen, C. P., Mochly-Rosen, D., and Kendig, J. J. (2004). Exaggerated nociceptive responses on morphine withdrawal: roles of protein kinase C epsilon and gamma. Pain 110, 281-289. doi: 10.1016/j.pain.2004.04.004
Szallasi, Z., and Blumberg, P. M. (1991). Prostratin, a nonpromoting phorbol ester, inhibits induction by phorbol 12-myristate 13-acetate of ornithine decarboxylase, edema, and hyperplasia in CD-1 mouse skin. Cancer Res. 51, 5355-5360
Tang, Y., Soroush, F., Sun, S., Liverani, E., Langston, J. C., Yang, Q., et al. (2018). Protein kinase C-delta inhibition protects blood-brain barrier from sepsis-induced vascular damage. J. Neuroinflammation 15:309. doi: 10.1186/s12974-018-1342-y
Torroglosa, A., Murillo-Carretero, M., Romero-Grimaldi, C., Matarredona, E. R., Campos-Caro, A., and Estrada, C. (2007). Nitric oxide decreases subventricular zone stem cell proliferation by inhibition of epidermal growth factor receptor and phosphoinositide-3-kinase/Akt pathway. Stem Cells 25, 88-97. doi: 10.1634/stemcells.2006-0131
Van Kolen, K., and Slegers, H. (2006). Atypical PKCzeta is involved in RhoA-dependent mitogenic signaling by the P2Y(12) receptor in C6 cells. FEBS J. 273, 1843-1854. doi: 10.1111/j.1742-4658.2006.05205.x
Wang, J., Gallagher, D., Devito, L. M., Cancino, G. I., Tsui, D., He, L., et al. (2012). Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell 11, 23-35. doi: 10.1016/j.stem.2012.03.016
Wang, Q. J., Bhattacharyya, D., Garfield, S., Nacro, K., Marquez, V. E., and Blumberg, P. M. (1999). Differential localization of protein kinase C d by phorbol esters and related compounds using a fusion protein with green fluorescent protein. J. Biol. Chem. 274, 37233-37239. doi: 10.1074/jbc.274.52.37233
Wang, Q. J., Fang, T.-W., Fenick, D., Garfield, S., Bienfait, B., Marquez, V. E., et al. (2000). The lipophilicity of phorbol esters as a critical factor in determining the pattern of translocation of protein kinase C d fused to green fluorescent protein. J. Biol. Chem. 275, 12136-12146. doi: 10.1074/jbc.275.16.12136
Wang, X., Hu, J., She, Y., Smith, G. M., and Xu, X. M. (2014). Cortical PKC inhibition promotes axonal regeneration of the corticospinal tract and forelimb functional recovery after cervical dorsal spinal hemisection in adult rats. Cereb Cortex 24, 3069-3079. doi: 10.1093/cercor/bht162
Watanabe, T., Ono, Y., Taniyama, Y., Hazama, K., Igarashi, K., Ogita, K., et al. (1992). Cell division arrest induced by phorbol ester in CHO cells overexpressing protein kinase C-delta subspecies. Proc. Natl. Acad. Sci. U.S.A. 89, 10159-10163. doi: 10.1073/pnas.89.21.10159
Zanin-Zhorov, A., Dustin, M. L., and Blazar, B. R. (2011). PKC-theta function at the immunological synapse: prospects for therapeutic targeting. Trends Immunol. 32, 358-363. doi: 10.1016/j.it.2011.04.007
Zhang, D., Anantharam, V., Kanthasamy, A., and Kanthasamy, A. G. (2007). Neuroprotective effect of protein kinase C delta inhibitor rottlerin in cell culture and animal models of Parkinson's disease. J. Pharmacol. Exp. Ther. 322, 913-922. doi: 10.1124/jpet.107.124669
