The “Memory Kinases”

Alkon, 1998, Time domains of neuronal Ca2+ signaling and associative memory: steps through a calexcitin, ryanodine receptor, K+ channel cascade, Trends Neurosci, 21, 529, 10.1016/S0166-2236(98)01277-6 Alkon, 2007, PKC signaling deficits: a mechanistic hypothesis for the origins of Alzheimer's disease, Trends Pharmacol Sci, 28, 51, 10.1016/j.tips.2006.12.002 Lipp, 2011, Protein kinase C: the “master” of calcium and lipid, Cold Spring Harb Perspect Biol, 3, a004556, 10.1101/cshperspect.a004556 Ohno, 1987, Tissue-specific expression of three distinct types of rabbit protein kinase C, Nature, 325, 161, 10.1038/325161a0 Breitkreutz, 2007, Protein kinase C family: on the crossroads of cell signaling in skin and tumor epithelium, J Cancer Res Clin Oncol, 11, 793, 10.1007/s00432-007-0280-3 Wetsel, 1992, Tissue and cellular distribution of the extended family of protein kinase C isoenzymes, J Cell Biol, 117, 121, 10.1083/jcb.117.1.121 Gong, 2012, Two protein kinase C isoforms, δ and ɛ, regulate energy homeostasis in mitochondria by transmitting opposing signals to the pyruvate dehydrogenase complex, FASEB J, 26, 3537, 10.1096/fj.11-197376 Dutil, 1998, Regulation of conventional protein kinase C isozymes by phosphoinositide-dependent kinase 1 (PDK-1), Curr Biol, 8, 1366, 10.1016/S0960-9822(98)00017-7 Le Good, 1998, Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1, Science, 281, 2042, 10.1126/science.281.5385.2042 Toker, 2000, Cellular signaling: pivoting around PDK-1, Cell, 2, 185, 10.1016/S0092-8674(00)00110-0 Edwards, 1997, Phosphorylation at conserved carboxyl-terminal hydrophobic motif regulates the catalytic and regulatory domains of protein kinase C, J Biol Chem, 272, 18382, 10.1074/jbc.272.29.18382 Facchinetti, 2008, The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C, EMBO J, 27, 1932, 10.1038/emboj.2008.120 Ikenoue, 2008, Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signaling, EMBO J, 27, 1919, 10.1038/emboj.2008.119 Hansra, 1996, 12-O-tetradecanoylphorbol-13-acetate-induced dephosphorylation of protein kinase Cα correlates with the presence of a membrane-associated protein phosphatase 2A heterotrimer, J Biol Chem, 271, 32785, 10.1074/jbc.271.51.32785 Hansra, 1999, Multisite dephosphorylation and desensitization of conventional protein kinase C isotypes, Biochem J, 342, 337, 10.1042/0264-6021:3420337 Newton, 2010, Protein kinase C. Poised to signal, Am J Physiol Endocrinol Metab, 298, E395, 10.1152/ajpendo.00477.2009 Keranen, 1995, Protein kinase C is regulated in vivo by three functionally distinct phosphorylations, Curr Biol, 5, 1394, 10.1016/S0960-9822(95)00277-6 Gysin, 1997, Phorbol-ester-activated protein kinase C-α lacking phosphorylation at Ser-657 is down-regulated by a mechanism involving dephosphorylation, Eur J Biochem, 249, 156, 10.1111/j.1432-1033.1997.t01-2-00156.x Gao, 2008, The phosphatase PHLPP controls the cellular levels of protein kinase C, J Biol Chem, 283, 6300, 10.1074/jbc.M707319200 Nalefski, 2001, Membrane binding kinetics of protein kinase C bII mediated by the C2 domain, Biochemistry, 40, 13216, 10.1021/bi010761u Dries, 2008, Kinetic analysis of the interaction of the C1 domain of protein kinase C with lipid membranes by stopped-flow spectroscopy, J Biol Chem, 283, 7885, 10.1074/jbc.M709943200 Scott, 2013, Electrostatic and hydrophobic interactions differentially tune membrane binding kinetics of the C2 domain of protein kinase Cα, J Biol Chem, 288, 16905, 10.1074/jbc.M113.467456 Kohout, 2002, C2 domains of protein kinase C isoforms α, β, and γ: activation parameters and calcium stoichiometries of the membrane-bound state, Biochemistry, 41, 11411, 10.1021/bi026041k Reither, 2006, PKCα: a versatile key for decoding the cellular calcium toolkit, J Cell Biol, 174, 521, 10.1083/jcb.200604033 Mott, 1996, The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site, Proc Natl Acad Sci USA, 93, 8312, 10.1073/pnas.93.16.8312 Zhou, 2002, Solution structure and functional analysis of the cysteine-rich C1 domain of kinase suppressor of Ras (KSR), J Mol Biol, 315, 435, 10.1006/jmbi.2001.5263 Colon-Gonzalez, 2006, C1 domains exposed: from diacylglycerol binding to protein–protein interactions, Biochim Biophys Acta, 1761, 827, 10.1016/j.bbalip.2006.05.001 Hirai, 2003, Protein kinase Cz (PKCz): activation mechanisms and cellular functions, J Biochem, 133, 1, 10.1093/jb/mvg017 Puls, 1997, Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein, Proc Natl Acad Sci USA, 94, 6191, 10.1073/pnas.94.12.6191 Qiu, 2000, A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCz signaling and cell transformation, Curr Biol, 10, 697, 10.1016/S0960-9822(00)00535-2 Emoto, 1995, Proteolytic activation of protein kinase C delta by an ICE-like protease in apoptotic cells, EMBO J, 14, 6148, 10.1002/j.1460-2075.1995.tb00305.x Kanthasamy, 2003, Role of proteolytic activation of protein kinase Cδ in oxidative stress-induced apoptosis, Antioxid Redox Signal, 5, 609, 10.1089/152308603770310275 Hernandez, 2003, Protein kinase Mζ synthesis from a brain mRNA encoding an independent protein kinase Cζ catalytic domain. Implications for the molecular mechanism of memory, J Biol Chem, 278, 40305, 10.1074/jbc.M307065200 Violin, 2003, A genetically encoded fluorescent reporter reveals oscillatory phosphorylation by protein kinase C, J Cell Biol, 161, 899, 10.1083/jcb.200302125 Mochly-Rosen, 1998, Anchoring proteins for protein kinase C: a means for isozyme selectivity, FASEB J, 1, 35, 10.1096/fasebj.12.1.35 Johnson, 1996, A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function, J Biol Chem, 271, 24962, 10.1074/jbc.271.40.24962 Smith, 1992, Inhibition of protein kinase C function by injection of intracellular receptor for the enzyme, Biochem Biophys Res Commun, 188, 1235, 10.1016/0006-291X(92)91363-U Wang, 1991, Protein kinase C phosphorylates the carboxyl terminus of the plasma membrane Ca2+-ATPase from human erythrocytes, J Biol Chem, 266, 9078, 10.1016/S0021-9258(18)31554-0 Xu, 2013, Hemorrhagic preconditioning improves vascular reactivity after hemorrhagic shock by activation of PKCα and PKCɛ via the adenosine A1 receptors in rats, J Trauma Acute Care Surg, 74, 1266, 10.1097/TA.0b013e31828dba35 Hornia, 1999, Antagonistic effects of protein kinase C α and δ on both transformation and phospholipase D activity mediated by the epidermal growth factor receptor, Mol Cell Biol, 19, 7672, 10.1128/MCB.19.11.7672 Han, 2002, Localization of phospholipase D1 to caveolin-enriched membrane via palmitoylation: implications for epidermal growth factor signaling, Mol Biol Cell, 13, 3976, 10.1091/mbc.E02-02-0100 Chen, 2004, Regulation of phospholipase D2 activity by protein kinase Ca, J Biol Chem, 279, 22076, 10.1074/jbc.M311033200 Lee, 2009, The roles of phospholipase in EGFR signaling, Biochim Biophys Acta, 1791, 862, 10.1016/j.bbalip.2009.04.007 Luo, 2003, Protein kinase C α phosphorylates and negatively regulates diacylglycerol kinase ζ, J Biol Chem, 278, 39542, 10.1074/jbc.M307153200 Imai, 2004, The plasma membrane translocation of diacylglycerol kinase δ1 is negatively regulated by conventional protein kinase C-dependent phosphorylation at Ser-22 and Ser-26 within the pleckstrin homology domain, Biochem J, 382, 957, 10.1042/BJ20040681 Kawabe, 1994, Differential activation of adenylyl cyclase by protein kinase C isoenzymes, J Biol Chem, 269, 16554, 10.1016/S0021-9258(19)89424-3 Zimmermann, 1996, Protein kinase C alters the responsiveness of adenylyl cyclases to G protein α and βγ subunits, J Biol Chem, 271, 27161, 10.1074/jbc.271.43.27161 Stevens, 1998, Regulation of the readily releasable vesicle pool by protein kinase C, Neuron, 21, 885, 10.1016/S0896-6273(00)80603-0 Dobransky, 2004, Protein kinase C isoforms differentially phosphorylate human choline acetyltransferase regulating its catalytic activity, J Neurochem, 279, 52059 Okada, 2004, Protein kinase associated with gating and closing transmission mechanisms in temporoammonic pathway, Neuropharmacology, 47, 485, 10.1016/j.neuropharm.2004.04.019 Rekart, 2005, Hippocampal-dependent memory is impaired in heterozygous GAP-43 knockout mice, Hippocampus, 15, 1, 10.1002/hipo.20045 Boehm, 2006, Synaptic incorporation of AMPA receptors during LTP is controlled by a PKC phosphorylation site on GluR1, Neuron, 51, 213, 10.1016/j.neuron.2006.06.013 Yang, 2010, Perisynaptic GluR2-lacking AMPA receptors control the reversibility of synaptic and spine modifications, Proc Natl Acad Sci USA, 107, 11999, 10.1073/pnas.0913004107 Chaki, 1994, Involvement of protein kinase C activation of acetylcholine release from rat hippocampal slices by minaprine, Neurochem Int, 24, 37, 10.1016/0197-0186(94)90127-9 Yamamoto, 2005, The linoleic acid derivative FR236924 facilitates hippocampal synaptic transmission by enhancing activity of presynaptic alpha7 acetylcholine receptors on the glutamatergic terminals, Neuroscience, 130, 207, 10.1016/j.neuroscience.2004.09.016 Lee, 2011, Protein kinase C epsilon modulates nicotine consumption and dopamine reward signals in the nucleus accumbens, Proc Natl Acad Sci USA, 108, 16080, 10.1073/pnas.1106277108 Exley, 2008, α6-Containing nicotinic acetylcholine receptors dominate the nicotine control of dopamine neurotransmission in nucleus accumbens, Neuropsychopharmacology, 33, 2158, 10.1038/sj.npp.1301617 Roberson, 1999, The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus, J Neurosci, 19, 4337, 10.1523/JNEUROSCI.19-11-04337.1999 Carr, 2002, Serotonin receptor activation inhibits sodium current and dendritic excitability in prefrontal cortex via a protein kinase C-dependent mechanism, J Neurosci, 22, 6846, 10.1523/JNEUROSCI.22-16-06846.2002 Carr, 2003, Transmitter modulation of slow, activity-dependent alterations in sodium channel availability endows neurons with a novel form of cellular plasticity, Neuron, 39, 793, 10.1016/S0896-6273(03)00531-2 Chen, 2005, Specific modulation of Na+ channels in hippocampal neurons by protein kinase C epsilon, J Neurosci, 25, 507, 10.1523/JNEUROSCI.4089-04.2005 Chen, 2006, Neuromodulation of Na+ channel slow inactivation via cAMP-dependent protein kinase and protein kinase C, Neuron, 49, 409, 10.1016/j.neuron.2006.01.009 González, 2002, Regulation of the neuronal glutamate transporter excitatory amino acid carrier-1 (EAAC1) by different protein kinase C subtypes, Mol Pharmacol, 62, 901, 10.1124/mol.62.4.901 Alkon, 1986, C-kinase activation prolongs CA-dependent inactivation of K currents, Biochem Biophys Res Commun, 134, 1245, 10.1016/0006-291X(86)90384-0 Farley, 1986, Protein kinase C activation induces conductance changes in Hermissenda photoreceptors like those seen in associative learning, Nature, 319, 220, 10.1038/319220a0 Song, 2011, Propofol inhibited the delayed rectifier potassium current (Ik) via activation of protein kinase C epsilon in rat parietal cortical neurons, Eur J Pharmacol, 653, 16, 10.1016/j.ejphar.2010.10.072 Lim, 2012, Protein kinase C stimulates HuD-mediated mRNA stability and protein expression of neurotrophic factors and enhances dendritic maturation of hippocampal neurons in culture, Hippocampus, 22, 2303, 10.1002/hipo.22048 Toni, 1997, Staurosporine but not chelerythrine inhibits regeneration in hippocampal organotypic cultures, Synapse, 27, 199, 10.1002/(SICI)1098-2396(199711)27:3<199::AID-SYN6>3.0.CO;2-8 Pilpel, 2004, Activation of PKC induces rapid morphological plasticity in dendrites of hippocampal neurons via Rac and Rho-dependent mechanisms, Eur J Neurosci, 19, 3151, 10.1111/j.0953-816X.2004.03380.x Adasme, 2011, Involvement of ryanodine receptors in neurotrophin-induced hippocampal synaptic plasticity and spatial memory formation, Proc Natl Acad Sci USA, 108, 3029, 10.1073/pnas.1013580108 Gundimeda, 2012, Green tea polyphenols precondition against cell death induced by oxygen–glucose deprivation via stimulation of laminin receptor, generation of reactive oxygen species, and activation of protein kinase Cɛ, J Biol Chem, 287, 34694, 10.1074/jbc.M112.356899 Sen, 2012, Apolipoprotein E3 (ApoE3) but not ApoE4 protects against synaptic loss through increased expression of protein kinase Cɛ, J Biol Chem, 287, 15947, 10.1074/jbc.M111.312710 Ron, 2012, Overexpression of PKMζ alters morphology and function of dendritic spines in cultured cortical neurons, Cereb Cortex, 22, 2519, 10.1093/cercor/bhr323 Schael, 2013, Casein kinase 2 phosphorylation of protein kinase C and casein kinase 2 substrate in neurons (PACSIN) 1 protein regulates neuronal spine formation, J Biol Chem, 288, 9303, 10.1074/jbc.M113.461293 Haydon, 2001, Glia: listening and talking, Nat Rev Neurosci, 2, 185, 10.1038/35058528 Hama, 2004, PKC signaling mediates global enhancement of excitatory synaptogenesis in neurons triggered by local contact with astrocytes, Neuron, 41, 405, 10.1016/S0896-6273(04)00007-8 Hongpaisan, 2007, A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC, Proc Natl Acad Sci USA, 104, 19571, 10.1073/pnas.0709311104 Hongpaisan, 2011, PKCɛ activation prevents synaptic loss, Aβ elevation, and cognitive deficits in Alzheimer's disease transgenic mice, J Neurosci, 31, 630, 10.1523/JNEUROSCI.5209-10.2011 Khadra, 2011, CD95 triggers orai1-mediated localized Ca2+ entry, regulates recruitment of protein kinase C (PKC) β2, and prevents death-inducing signaling complex formation, Proc Natl Acad Sci USA, 108, 19072, 10.1073/pnas.1116946108 Basu, 2010, Two faces of protein kinase Cδ: the contrasting roles of PKCδ in cell survival and cell death, Sci World J, 10, 2272, 10.1100/tsw.2010.214 Spaeth, 2010, A model for sealing plasmalemmal damage in neuron and other eukaryotic cells, J Neurosci, 30, 15790, 10.1523/JNEUROSCI.4155-10.2010 Crisanti, 2005, Aspirin prevention of NMDA-induced neuronal death by direct protein kinase Cζ inhibition, J Neurochem, 93, 1587, 10.1111/j.1471-4159.2005.03157.x Baines, 2002, Mitochondrial PKCepsilon and MAPK form signaling modules in the murine heart: enhanced mitochondrial PKCepsilon-MAPK interactions and differential MAPK activation in PKCepsilon-induced cardioprotection, Circ Res, 8, 390, 10.1161/01.RES.0000012702.90501.8D Kim, 2007, Ischemic preconditioning via ɛ protein kinase C activation requires cyclooxygenase-2 activation in vitro, Neuroscience, 145, 931, 10.1016/j.neuroscience.2006.12.063 Dave, 2008, Ischemic preconditioning targets the respiration of synaptic mitochondria via protein kinase Cɛ, J Neurosci, 28, 4172, 10.1523/JNEUROSCI.5471-07.2008 Cosentino-Gomes, 2012, Cell signaling through protein kinase C oxidation and activation, Int J Mol Sci, 13, 10697, 10.3390/ijms130910697 Huang, 2012, Neuroprotective effects of reactive oxygen species mediated by BDNF-independent activation of TrkB, J Neurosci, 32, 15521, 10.1523/JNEUROSCI.0755-12.2012 Ardehali, 2006, Signaling mechanisms in ischemic preconditioning. Interaction of PKCɛ and MitoK(ATP) in the inner membrane of mitochondria, Circ Res, 99, 798, 10.1161/01.RES.0000247029.31997.a4 Raval, 2007, ɛPKC phosphorylates the mitochondrial K+ (ATP) channel during induction of ischemic preconditioning in the rat hippocampus, Brain Res, 1184, 345, 10.1016/j.brainres.2007.09.073 Lømo, 1966, Frequency potentiation of excitatory synaptic activity in the dentate area of the hippocampal formation, Acta Physiol Scand, 68, 128 Bliss, 1973, Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path, J Physiol, 232, 331, 10.1113/jphysiol.1973.sp010273 Ramakers, 1997, Protein kinase C in synaptic plasticity: changes in the in situ phosphorylation state of identified pre- and postsynaptic substrates, Prog Neuropsychopharmacol Biol Psychiatry, 21, 455, 10.1016/S0278-5846(97)00013-4 Kim, 2012, Bryostatin-1 promotes long-term potentiation via activation of PKCα and PKCɛ in the hippocampus, Hippocampus, 226, 348 Meiri, 1998, Memory and long-term potentiation (LTP) dissociated: normal spatial memory despite CA1 LTP elimination with Kv1.4 antisense, Proc Natl Acad Sci USA, 95, 15037, 10.1073/pnas.95.25.15037 Zamanillo, 1999, Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning, Science, 284, 1805, 10.1126/science.284.5421.1805 Weeber, 2000, A role for the beta isoform of protein kinase C in fear conditioning, J Neurosci, 20, 5906, 10.1523/JNEUROSCI.20-16-05906.2000 Ling, 2002, Protein kinase Mζ is necessary and sufficient for LTP maintenance, Nat Neurosci, 5, 295, 10.1038/nn829 Pang, 2004, Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity, Science, 306, 487, 10.1126/science.1100135 Sacktor, 1993, Persistent activation of the ζ isoform of protein kinase C in the maintenance of long-term potentiation, Proc Natl Acad Sci USA, 90, 8342, 10.1073/pnas.90.18.8342 Osten, 1996, Protein synthesis-dependent formation of protein kinase Mζ in long-term potentiation, J Neurosci, 16, 2444, 10.1523/JNEUROSCI.16-08-02444.1996 Kelly, 2007, Regulation of protein kinase Mζ synthesis by multiple kinases in long-term potentiation, J Neurosci, 27, 3439, 10.1523/JNEUROSCI.5612-06.2007 Kelly, 2006, Actin polymerization regulates the synthesis of PKMζ in LTP, Neuropharmacology, 52, 41, 10.1016/j.neuropharm.2006.07.002 Sacktor, 2008, PKMzeta, LTP maintenance, and the dynamic molecular biology of memory storage, Prog Brain Res, 169, 27, 10.1016/S0079-6123(07)00002-7 Yao, 2012, Matching biochemical and functional efficacies confirm ZIP as a potent competitive inhibitor of PKMζ in neurons, Neuropharmacology, 64, 37, 10.1016/j.neuropharm.2012.07.018 Shao, 2011, PKMζ is necessary and sufficient for synaptic clustering of PSD-95, Hippocampus, 22, 1501, 10.1002/hipo.20996 Yoshii, 2011, TrkB and protein kinase Mζ regulate synaptic localization of PSD-95 in developing cortex, J Neurosci, 31, 11894, 10.1523/JNEUROSCI.2190-11.2011 Yao, 2008, PKMζ maintains late long-term potentiation by N-ethylmaleimide-sensitive factor/GluR2-dependent trafficking of postsynaptic AMPA receptors, J Neurosci, 28, 7820, 10.1523/JNEUROSCI.0223-08.2008 Migues, 2010, PKMζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking, Nat Neurosci, 13, 630, 10.1038/nn.2531 Sacktor, 2011, How does PKMζ maintain long-term memory?, Nat Rev Neurosci, 12, 9, 10.1038/nrn2949 Kim, 2004, PDZ domain proteins of synapses, Nat Rev Neurosci, 5, 771, 10.1038/nrn1517 van Zundert, 2004, Receptor compartmentalization and trafficking at glutamate synapses: a developmental proposal, Trends Neurosci, 27, 428, 10.1016/j.tins.2004.05.010 Colombo, 1997, Spatial memory is related to hippocampal subcellular concentrations of calcium-dependent protein kinase C isoforms in young and aged rats, Proc Natl Acad Sci USA, 94, 14195, 10.1073/pnas.94.25.14195 Sun, 2005, Dual effects of bryostatin-1 on spatial memory and depression, Eur J Pharmacol, 512, 43, 10.1016/j.ejphar.2005.02.028 Rochefort, 2011, Cerebellum shapes hippocampal spatial code, Science, 334, 385, 10.1126/science.1207403 Schreurs, 1996, Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic potentials results from a classical conditioning procedure in the rabbit cerebellar slice, J Neurophysiol, 75, 1051, 10.1152/jn.1996.75.3.1051 Schreurs, 1997, Dendritic excitability microzones and occluded long-term depression after classical conditioning of the rabbit's nictitating membrane response, J Neurophysiol, 77, 86, 10.1152/jn.1997.77.1.86 Olds, 1994, Lateralization of membrane-associated protein-kinase-C in rat piriform cortex—specific to operant training cues in the olfactory modality, Behav Brain Res, 61, 37, 10.1016/0166-4328(94)90006-X Ahi, 2004, The role of hippocampal signaling cascades in consolidation of fear memory, Behav Brain Res, 149, 17, 10.1016/S0166-4328(03)00207-9 Li, 2011, Inhibition of PKMzeta in nucleus accumbens core abolishes long-term drug reward memory, J Neurosci, 31, 5436, 10.1523/JNEUROSCI.5884-10.2011 Nimitvilai, 2012, Reversal of dopamine inhibition of dopaminergic neurons of the ventral terminal area is mediated by protein kinase C, Neuropharmacology, 37, 543 Ping, 2012, Essential role of protein kinase C in morphine-induced rewarding memory, Neuropharmacology, 62, 959, 10.1016/j.neuropharm.2011.10.001 de Quervain, 2012, PKCα is genetically linked to memory capacity in healthy subjects and to risk for posttraumatic stress disorder in genocide survivors, Proc Natl Acad Sci USA, 109, 8746, 10.1073/pnas.1200857109 Van der Zee, 1995, Alterations in the immuno-reactivity for muscarinic acetylcholine receptors and colocalized PKC gamma in mouse hippocampus induced by spatial discrimination learning, Hippocampus, 5, 349, 10.1002/hipo.450050408 Van der Zee, 1992, Changes in PKC gamma immunoreactivity in mouse hippocampus induced by spatial discrimination learning, J Neurosci, 12, 4808, 10.1523/JNEUROSCI.12-12-04808.1992 Abeliovich, 1993, Modified hippocampal long-term potentiation in PKC gammamutant mice, Cell, 75, 1253, 10.1016/0092-8674(93)90613-U Abeliovich, 1993, PKC gamma mutant mice exhibit mild deficits in spatial and contextual learning, Cell, 75, 1263, 10.1016/0092-8674(93)90614-V Malmberg, 1997, Preserved acute pain and reduced neuropathic pain in mice lacking PKCgamma, Science, 278, 279, 10.1126/science.278.5336.279 Bowers, 2000, Mice lacking PKC gamma exhibit decreased anxiety, Behav Genet, 30, 111, 10.1023/A:1001951104208 Hongpaisan, 2013, PKC activation during training restores mushroom spine synapses and memory in the aged rat, Neurobiol Dis, 55, 44, 10.1016/j.nbd.2013.03.012 Shema, 2011, Enhancement of consolidated long-term memory by overexpression of protein kinase Mzeta in the neocortex, Science, 331, 1207, 10.1126/science.1200215 Sacktor, 2012, Memory maintenance by PKMzeta—an evolutionary perspective, Mol Brain, 5, 31, 10.1186/1756-6606-5-31 Glanzman, 2013, PKM and the maintenance of memory, Biol Rep, 5, 4 Serrano, 2005, Persistent phosphorylation by protein kinase Mζ maintains late-phase long-term potentiation, J Neurosci, 25, 1979, 10.1523/JNEUROSCI.5132-04.2005 Cai, 2011, Protein kinase M maintains long-term sensitization and long-term facilitation in Aplysia, J Neurosci, 31, 6421, 10.1523/JNEUROSCI.4744-10.2011 Serrano, 2008, PKMζ maintains spatial, instrumental, and classically conditioned long-term memories, PLoS Biol, 6, 2698, 10.1371/journal.pbio.0060318 Hardt, 2010, PKMzeta maintains 1-day- and 6-day-old long-term object location but not object identity memory in dorsal hippocampus, Hippocampus, 20, 691 Barry, 2012, Inhibition of PKMζ disrupts the stable spatial discharge of hippocampal place cells in a familiar environment, J Neurosci, 32, 13753, 10.1523/JNEUROSCI.0319-12.2012 Madronal, 2010, PKMζ inhibition reverses learning-induced increases in hippocampal synaptic strength and memory during trace eyeblink conditioning, PLoS One, 5, e10400, 10.1371/journal.pone.0010400 Kwapis, 2009, Protein kinase Mzeta maintains fear memory in the amygdala but not in the hippocampus, Behav Neurosci, 123, 844, 10.1037/a0016343 Gamiz, 2011, Intra-amygdala ZIP injections impair the memory of learned active avoidance responses and attenuate conditioned taste-aversion acquisition in rats, Learn Mem, 18, 529, 10.1101/lm.2253311 Kwapis, 2012, Intra-amygdala infusion of the protein kinase Mzeta inhibitor ZIP disrupts foreground context fear memory, Neurobiol Learn Mem, 98, 148, 10.1016/j.nlm.2012.05.003 Crespo, 2012, Activation of PKCzeta and PKMzeta in the nucleus accumbens core is necessary for the retrieval, consolidation and reconsolidation of drug memory, PLoS One, 7, e30502, 10.1371/journal.pone.0030502 Shabashov, 2012, Inactivation of PKMzeta in the NAc shell abolished cocaine-conditioned reward, J Mol Neurosci, 47, 546, 10.1007/s12031-011-9671-7 Pauli, 2012, Inhibiting PKMzeta reveals dorsal lateral and dorsal medial striatum store the different memories needed to support adaptive behavior, Learn Mem, 19, 307, 10.1101/lm.025148.111 Shema, 2007, Rapid erasure of long-term memory associations in cortex by an inhibitor of PKMζ, Science, 317, 951, 10.1126/science.1144334 Shema, 2009, Boundary conditions for the maintenance of memory by PKMζ in neocortex, Learn Mem, 16, 122, 10.1101/lm.1183309 Sacco, 2010, Role of secondary sensory cortices in emotional memory storage and retrieval in rats, Science, 329, 649, 10.1126/science.1183165 He, 2011, PKMzeta maintains drug reward and aversion memory in the basolateral amygdala and extinction memory in the infralimbic cortex, Neuropsychopharmacology, 36, 1972, 10.1038/npp.2011.63 von Kraus, 2010, Erasing sensorimotor memories via PKMzeta inhibition, PLoS One, 5, e11125, 10.1371/journal.pone.0011125 Pastalkova, 2006, Storage of spatial information by the maintenance mechanism of LTP, Science, 313, 1141, 10.1126/science.1128657 Xue, 2012, A memory retrieval-extinction procedure to prevent drug craving and relapse, Science, 336, 241, 10.1126/science.1215070 Moncada, 2008, PKMzeta inactivation induces spatial familiarity, Learn Mem, 15, 810, 10.1101/lm.1139508 Crary, 2006, Atypical protein kinase C in neurodegenerative disease I: PKMζ aggregates with limbic neurofibrillary tangles and AMPA receptors in Alzheimer disease, J Neuropathol Exp Neurol, 65, 319, 10.1097/01.jnen.0000218442.07664.04 Volk, 2013, PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory, Nature, 493, 420, 10.1038/nature11802 Lee, 2013, PrKcz null mice show normal learning and memory, Nature, 493, 416, 10.1038/nature11803 Mochly-Rosen, 2012, Protein kinase C, an elusive therapeutic target?, Nat Rev Drug Discov, 11, 937, 10.1038/nrd3871 Roffey, 2009, Protein kinase C intervention—the state of play, Curr Opin Cell Biol, 21, 268, 10.1016/j.ceb.2009.01.019 Fabian, 2005, A small molecule-kinase interaction map for clinical kinase inhibitors, Nat Biotechnol, 23, 329, 10.1038/nbt1068 Kang, 2012, Intracellular interaction of interleukin (IL)-32α with protein kinase Cɛ (PKCɛ) and STAT3 protein augments IL-6 production in THP-1 promonocytic cells, J Biol Chem, 287, 35556, 10.1074/jbc.M112.400911 Okuwa, 2012, Sphingosine suppresses mesothelioma cell proliferation by inhibiting PKC-δ and inducing cell cycle arrest at the G(0)/G(1) phase, Cell Physiol Biochem, 30, 995, 10.1159/000341476 Leppänen, 2013, Down-regulation of protein kinase Cδ inhibits inducible nitric oxide synthase expression through IRF1, PLoS One, 8, e52741, 10.1371/journal.pone.0052741 Soltoff, 2007, Rottlerin: an inappropriate and ineffective inhibitor of PKCδ, Trends Pharmacol Sci, 28, 453, 10.1016/j.tips.2007.07.003 Davies, 2000, Specificity and mechanism of action of some commonly used protein kinase inhibitors, Biochem J, 351, 95, 10.1042/0264-6021:3510095 Whitson, 2008, Spheciosterol sulfates, PKCzeta inhibitors from a Philippine sponge Spheciospongia sp, J Nat Prod, 71, 1213, 10.1021/np8001628 Herbert, 1990, Chelerythrine is a potent and specific inhibitor of protein kinase C, Biochem Biophys Res Commun, 172, 993, 10.1016/0006-291X(90)91544-3 Kobayashi, 1989, Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C, Biochem Biophys Res Commun, 159, 548, 10.1016/0006-291X(89)90028-4 Bruns, 1991, Inhibition of protein kinase C by calphostin C is light-dependent, Biochem Biophys Res Commun, 176, 288, 10.1016/0006-291X(91)90922-T Bonini, 2007, On the participation of hippocampal PKC in acquisition, consolidation and reconsolidation of spatial memory, Neuroscience, 147, 37, 10.1016/j.neuroscience.2007.04.013 Abrial, 2013, Protein kinase C regulates mood-related behaviors and adult hippocampal cell proliferation in rats, Prog Neuropsychopharmacol Biol Psychiatry, 43, 40, 10.1016/j.pnpbp.2012.11.015 Zarate, 2009, Proetin kinase C inhibitors: rationale for use and potential in the treatment of bipolar disorder, CNS Drugs, 23, 569, 10.2165/00023210-200923070-00003 Koponen, 2000, Induction of protein kinase Cdelta subspecies in neurons and microglia after transient global brain ischemia, J Cereb Blood Flow Metab, 20, 93, 10.1097/00004647-200001000-00013 Miettinen, 1996, Specific induction of protein kinase C delta subspecies after transient middle cerebral artery occlusion in the rat brain: inhibition by MK-801, J Neurosci, 16, 6236, 10.1523/JNEUROSCI.16-19-06236.1996 Dave, 2011, Activation of protein kinase C delta following cerebral ischemia leads to release of cytochrome C from the mitochondria via bad pathway, PLoS One, 6, e22057, 10.1371/journal.pone.0022057 Phan, 2002, Salvaging the ischaemic penumbra: more than just reperfusion?, Clin Exp Pharmacol Physiol, 29, 1, 10.1046/j.1440-1681.2002.03609.x Bright, 2004, Protein kinase C delta mediates cerebral reperfusion injury in vivo, J Neurosci, 24, 6880, 10.1523/JNEUROSCI.4474-03.2004 Kanno, 2006, The linoleic acid derivative DCP-LA selectively activates PKC-epsilon, possibly binding to the phosphatidylserine binding site, J Lipid Res, 47, 1146, 10.1194/jlr.M500329-JLR200 Nelson, 2009, Neuroprotective versus tumorigenic protein kinase C activators, Trends Biochem Sci, 34, 136, 10.1016/j.tibs.2008.11.006 Sun, 2008, Poststroke neuronal rescue and synaptogenesis mediated in vivo by protein kinase C in adult brains, Proc Natl Acad Sci USA, 105, 13620, 10.1073/pnas.0805952105 Sun, 2009, Postischemic PKC activation rescues retrograde and anterograde long-term memory, Proc Natl Acad Sci USA, 106, 14676, 10.1073/pnas.0907842106 Sun, 2013, Selective activation of protein kinase Cɛ in mitochondria is neuroprotective in vitro and reduces focal ischemic brain injury in mice, J Neurosci Res, 91, 799, 10.1002/jnr.23186 Postina, 2004, A disintegrin-metalloproteinase prevents amyloid plaque formation and hippocampal defects in an Alzheimer disease mouse model, J Clin Invest, 113, 1456, 10.1172/JCI20864 Desdouits, 1996, Amyloid alpha peptide formation in cell-free preparations. Regulation by protein kinase C, calmodulin, and calcineurin, J Biol Chem, 271, 24670, 10.1074/jbc.271.40.24670 Pakask, 2001, Human amyloid-beta causes changes in the levels of endothelial protein kinase C and its alpha isoform in vitro, Neurochem Int, 41, 409, 10.1016/S0197-0186(02)00026-8 Lee, 2004, Amyloid beta peptide directly inhibits PKC activation, Mol Cell Neurosci, 26, 222, 10.1016/j.mcn.2003.10.020 Cordey, 2003, Estrogen activates protein kinase C in neurons: role in neuroprotection, J Neurochem, 84, 1340, 10.1046/j.1471-4159.2003.01631.x Govoni, 1993, Cytosol protein kinase C downregulation in fibroblasts from Alzheimer's disease patients, Neurology, 43, 2581, 10.1212/WNL.43.12.2581 Liu, 2011, RACK1 is involved in beta-amyloid impairment of muscarinic regulation of GABAergic transmission, Neurobiol Aging, 32, 1818, 10.1016/j.neurobiolaging.2009.10.017 Fahrenholz, 2007, Alpha-secretase as a therapeutic target, Curr Alzheimer Res, 4, 412, 10.2174/156720507781788837 Lichtenthaler, 2011, Alpha-secretase in Alzheimer's disease: molecular identity, regulation and therapeutic potential, J Neurochem, 116, 10, 10.1111/j.1471-4159.2010.07081.x Jorissen, 2010, The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortex, J Neurosci, 30, 4833, 10.1523/JNEUROSCI.5221-09.2010 Kuhn, 2010, ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons, EMBO J, 29, 3020, 10.1038/emboj.2010.167 Sisodia, 1992, Beta-amyloid precursor protein cleavage by a membrane-bound protease, Proc Natl Acad Sci USA, 89, 6075, 10.1073/pnas.89.13.6075 Skovronsky, 2000, Protein kinase C-dependent alpha-secretase competes with beta-secretase for cleavage of amyloid-beta precursor protein in the trans-golgi network, J Biol Chem, 275, 2568, 10.1074/jbc.275.4.2568 Asiedu, 2011, Spinal protein kinase Mζ underlies the maintenance mechanism of persistent nociceptive sensitization, J Neurosci, 31, 6646, 10.1523/JNEUROSCI.6286-10.2011 Koo, 1994, Evidence that production and release of amyloid beta-protein involves the endocytic pathway, J Biol Chem, 269, 17386, 10.1016/S0021-9258(17)32449-3 Vassar, 1999, Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE, Science, 286, 735, 10.1126/science.286.5440.735 Holmes, 2008, Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial, Lancet, 372, 216, 10.1016/S0140-6736(08)61075-2 Schenk, 2005, A beta immunotherapy: lessons learned for potential treatment of Alzheimer's disease, Neurodegener Dis, 2, 255, 10.1159/000090365 Serrano-Pozo, 2010, Beneficial effect of human anti-amyloid-beta active immunization on neurite morphology and tau pathology, Brain, 133, 1312, 10.1093/brain/awq056 Lilly. Lilly Halts Development of Semagacestat for Alzheimer's Disease Based on Preliminary Results of Phase III Clinical Trials. http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=499794; 2011. Accessed March 13, 2012. Etcheberrigaray, 2004, Therapeutic effects of PKC activators in Alzheimer's disease transgenic mice, Proc Natl Acad Sci USA, 101, 11141, 10.1073/pnas.0403921101 Khan, 2009, A cellular model of Alzheimer's disease therapeutic efficacy: PKC activation reverses Abeta-induced biomarker abnormality on cultured fibroblasts, Neurobiol Dis, 34, 332, 10.1016/j.nbd.2009.02.003 Nelson, 2009, Reduction of beta-amyloid levels by novel PKC epsilon activators, J Biol Chem, 284, 34514, 10.1074/jbc.M109.016683 Kim, 2011, Protein kinase C-regulated Aβ production and clearance, Int J Alzheimers Dis, 2011, 857368 Zhu, 2001, Protein kinase Cɛ suppresses Aβ production and promotes activation of α-secretase, Biochem Biophys Res Commun, 285, 997, 10.1006/bbrc.2001.5273 Choi, 2006, PKCɛ increases endothelin converting enzyme activity and reduces amyloid plaque pathology in transgenic mice, Proc Natl Acad Sci USA, 103, 8215, 10.1073/pnas.0509725103 Eckman, 2001, Degradation of the Alzheimer's amyloid β peptide by endothelin-converting enzyme, J Biol Chem, 276, 24540, 10.1074/jbc.M007579200 Eckman, 2003, Alzheimer's disease β-amyloid peptide is increased in mice deficient in endothelin-converting enzyme, J Biol Chem, 278, 2081, 10.1074/jbc.C200642200 Funalot, 2004, Endothelin-converting enzyme-1 is expressed in human cerebral cortex and protects against Alzheimer's disease, Mol Psychiatry, 9, 1122, 10.1038/sj.mp.4001584 Kozikowski, 2003, New amide-bearing benzolactam-based protein kinase C modulators induce enhanced secretion of the amyloid precursor protein metabolic sAPPalpha, J Med Chem, 46, 364, 10.1021/jm020350r Lahn, 2004, Protein kinase C-alpha in prostate cancer, BJU Int, 93, 1076, 10.1111/j.1464-410X.2003.04784.x Lavoie, 1999, Regulation of glycogen synthase in rat hepatocytes. Evidence for multiple signaling pathway, J Biol Chem, 274, 28279, 10.1074/jbc.274.40.28279 Cho, 2004, Glycogen synthase kinase 3 beta induces caspase-cleaved tau aggregation in situ, J Biol Chem, 279, 54716, 10.1074/jbc.M403364200 Mailliot, 2000, Pathological tau phenotypes. The weight of mutations, polymorphisms, and differential neuronal vulnerabilities, Ann NY Acad Sci, 920, 107, 10.1111/j.1749-6632.2000.tb06911.x Mandelkow, 1998, Tau in Alzheimer's disease, Trends Cell Biol, 8, 425, 10.1016/S0962-8924(98)01368-3 Liu, 2012, Identification of differentially expressed microRNAs and their PKC-isoform specific gene network prediction during hypoxic preconditioning and focal cerebral ischemia of mice, J Neurochem, 120, 830, 10.1111/j.1471-4159.2011.07624.x Di-Capua, 2003, Protein kinase C-ɛ is involved in the adenosine-activated signal transduction pathway conferring protection against ischemia–reperfusion injury in primary rat neuronal cultures, J Neurochem, 84, 409, 10.1046/j.1471-4159.2003.01563.x Raval, 2003, ɛPKC is required for the induction of tolerance by ischemic and NMDA-mediated preconditioning in the organotypic hippocampal slice, J Neurosci, 23, 384, 10.1523/JNEUROSCI.23-02-00384.2003 Takeishi, 2000, Transgenic overexpression of constitutively active protein kinase C epsilon causes concentric cardiac hypertrophy, Circ Res, 86, 1218, 10.1161/01.RES.86.12.1218 Wang, 2011, Activation of epsilon protein kinase C-mediated anti-apoptosis is involved in rapid tolerance induced by electroacupuncture pretreatment through cannabinoid receptor type 1, Stroke, 42, 389, 10.1161/STROKEAHA.110.597336 Dumont, 2012, Protein kinase Cɛ activity induces anti-inflammatory and anti-apoptotic genes via an ERK1/2- and NF-κB-dependent pathway to enhance vascular protection, Biochem J, 447, 193, 10.1042/BJ20120574 McCarthy, 2011, PKCɛ promotes cardiac mitochondrial and metabolic adaptation to chronic hypobaric hypoxia by GSK3β inhibition, J Cell Physiol, 226, 2457, 10.1002/jcp.22592 Janes, 2005, Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans, Cell, 123, 291, 10.1016/j.cell.2005.08.014 Pruessmeyer, 2009, The good, the bad and the ugly substrates for ADAM10 and ADAM17 in brain pathology, inflammation and cancer, Semin Cell Dev Biol, 20, 164, 10.1016/j.semcdb.2008.09.005 Reiss, 2009, The “a disintegrin and metalloprotease” (ADAM) family of sheddases: physiological and cellular functions, Semin Cell Dev Biol, 20, 126, 10.1016/j.semcdb.2008.11.002 Meneghini, 2013, High-mobility group box-1 protein and β-amyloid oligomers promote neuronal differentiation of adult hippocampal neural progenitors via receptor for advanced glycation end product/nuclear factor-κB axis: relevance for Alzheimer's disease, J Neurosci, 33, 6047, 10.1523/JNEUROSCI.2052-12.2013 Ma, 2013, Control of nutrient stress-induced metabolic reprogramming by PKCζ in tumorigenesis, Cell, 152, 599, 10.1016/j.cell.2012.12.028 McGaugh, 2002, Memory consolidation and the amygdala: a systems perspective, Trends Neurosci, 25, 456, 10.1016/S0166-2236(02)02211-7 McGaugh, 2000, Memory—a century of consolidation, Science, 287, 248, 10.1126/science.287.5451.248 Ranganath, 2010, A unified framework for the functional organization of the medial temporal lobes and the phenomenology of episodic memory, Hippocampus, 20, 1263, 10.1002/hipo.20852 Rodrigues, 2004, Molecular mechanisms underlying emotional learning and memory in the lateral amygdala, Neuron, 44, 75, 10.1016/j.neuron.2004.09.014 Mao, 1995, Increases in protein kinase C gamma immunoreactivity in the spinal cord dorsal horn of rats with painful mononeuropathy, Neurosci Lett, 198, 75, 10.1016/0304-3940(95)11975-3 Miletic, 2000, Loose ligation of the rat sciatic nerve is accompanied by changes in the subcellular content of protein kinase C beta II and gamma in the spinal dorsal horn, Neurosci Lett, 288, 199, 10.1016/S0304-3940(00)01237-4 Zhou, 2003, State-dependent phosphorylation of epsilon-isozyme of protein kinase C in adult rat dorsal root ganglia after inflammation and nerve injury, J Neurochem, 85, 571, 10.1046/j.1471-4159.2003.01675.x Wu, 2012, PKCɛ phosphorylation of the sodium channel Nav1.8 increases channel function and produces mechanical hyperalgesia in mice, J Clin Invest, 122, 1306, 10.1172/JCI61934 Laferriere, 2011, PKMζ is essential for spinal plasticity underlying the maintenance of persistent pain, Mol Pain, 7, 99, 10.1186/1744-8069-7-99 Ho, 2012, Protein kinase Mζ is necessary for cocaine-induced synaptic potentiation in the ventral tegmental area, Biol Psychiatry, 71, 706, 10.1016/j.biopsych.2011.10.031 Narita, 2001, Involvement of protein kinase Cgamma isoform in morphine-induced reinforcing effects, Neuroscience, 103, 309, 10.1016/S0306-4522(00)00572-8 Hasham, 1997, Glutamate-mediated activation of protein kinase C in hippocampal neurons, Neurosci Lett, 228, 115, 10.1016/S0304-3940(97)00382-0 Maurice, 2001, D1/D5 dopamine receptor activation differentially modulates rapidly inactivating and persistent sodium currents in prefrontal cortex, J Neurosci, 21, 2268, 10.1523/JNEUROSCI.21-07-02268.2001 Sato, 2004, Facilitative effect of a novel AVP fragment analog, NC-1900, on memory retention and recall in mice, Peptides, 25, 1139, 10.1016/j.peptides.2004.04.001 Cole, 1988, Decreased levels of protein kinase C in Alzheimer brain, Brain Res, 452, 165, 10.1016/0006-8993(88)90021-2 Paula-Lima, 2011, Amyloid β-peptide oligomers stimulate RyR-mediated Ca2+ release inducing mitochondrial fragmentation in hippocampal neurons and prevent RyR-mediated dendritic spine remodeling produced by BDNF, Antioxid Redox Signal, 14, 1209, 10.1089/ars.2010.3287