Gene Symbol: Prkcz
Description: protein kinase C, zeta
Alias: 14-3-3-zetaisoform, Pkcz, r14-3-3, protein kinase C zeta type, 14 - 3 - 3 - zeta isoform, nPKC-zeta
Species: rat
Products:     Prkcz

Top Publications

  1. Berra E, Diaz Meco M, Lozano J, Frutos S, Municio M, Sanchez P, et al. Evidence for a role of MEK and MAPK during signal transduction by protein kinase C zeta. EMBO J. 1995;14:6157-63 pubmed
    ..The importance of MEK/MAPK in the signalling mechanisms activated by zeta PKC was addressed by using the activation of a kappa B-dependent promoter as a biological read-out of zeta PKC. ..
  2. Moreno L, Frazziano G, Cogolludo A, Cobeño L, Tamargo J, Perez Vizcaino F. Role of protein kinase Czeta and its adaptor protein p62 in voltage-gated potassium channel modulation in pulmonary arteries. Mol Pharmacol. 2007;72:1301-9 pubmed
    ..These observations identify PKCzeta and/or p62 as potential therapeutic targets for the treatment of pulmonary hypertension. ..
  3. Martin P, Villares R, Rodriguez Mascarenhas S, Zaballos A, Leitges M, Kovac J, et al. Control of T helper 2 cell function and allergic airway inflammation by PKCzeta. Proc Natl Acad Sci U S A. 2005;102:9866-71 pubmed
    ..Moreover, PKCzeta-/- mice display dramatic inhibition of ovalbumin-induced allergic airway disease, strongly suggesting that PKCzeta can be a therapeutic target in asthma. ..
  4. Etienne Manneville S, Hall A. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell. 2001;106:489-98 pubmed
    ..Localized PKCzeta activity, acting through the microtubule motor protein dynein, is required for all aspects of induced polarity in these cells. ..
  5. Steiler T, Galuska D, Leng Y, Chibalin A, Gilbert M, Zierath J. Effect of hyperglycemia on signal transduction in skeletal muscle from diabetic Goto-Kakizaki rats. Endocrinology. 2003;144:5259-67 pubmed
    ..The long-term consequence of elevated PDK-1 and PKC phosphorylation/activity should be considered in the context of diabetes mellitus, as hyperglycemia is a clinical feature of this disease. ..
  6. Serrano P, Friedman E, Kenney J, Taubenfeld S, Zimmerman J, Hanna J, et al. PKMzeta maintains spatial, instrumental, and classically conditioned long-term memories. PLoS Biol. 2008;6:2698-706 pubmed publisher
  7. Sajikumar S, Navakkode S, Sacktor T, Frey J. Synaptic tagging and cross-tagging: the role of protein kinase Mzeta in maintaining long-term potentiation but not long-term depression. J Neurosci. 2005;25:5750-6 pubmed
    ..Thus, PKMzeta is the first LTP-specific PRP and is critical for the transformation of early into late LTP during both synaptic tagging and cross-tagging. ..
  8. Büther K, Plaas C, Barnekow A, Kremerskothen J. KIBRA is a novel substrate for protein kinase Czeta. Biochem Biophys Res Commun. 2004;317:703-7 pubmed
    ..Our studies presented here revealed that KIBRA is a novel substrate for PKCzeta and suggest that PKCzeta phosphorylation may regulate the cellular function of KIBRA. ..
  9. Ling D, Benardo L, Serrano P, Blace N, Kelly M, Crary J, et al. Protein kinase Mzeta is necessary and sufficient for LTP maintenance. Nat Neurosci. 2002;5:295-6 pubmed

More Information


  1. Ono Y, Fujii T, Ogita K, Kikkawa U, Igarashi K, Nishizuka Y. The structure, expression, and properties of additional members of the protein kinase C family. J Biol Chem. 1988;263:6927-32 pubmed
    ..Northern blot analysis suggests that the new members of protein kinase C exist in the brain and some other tissues. ..
  2. Shema R, Haramati S, Ron S, Hazvi S, Chen A, Sacktor T, et al. Enhancement of consolidated long-term memory by overexpression of protein kinase Mzeta in the neocortex. Science. 2011;331:1207-10 pubmed publisher
    ..Here, we report that overexpression in the rat neocortex of the protein kinase C isozyme protein kinase M? (PKM?) enhances long-term memory, whereas a dominant negative PKM? disrupts memory, even long after memory has been formed. ..
  3. Shema R, Sacktor T, Dudai Y. Rapid erasure of long-term memory associations in the cortex by an inhibitor of PKM zeta. Science. 2007;317:951-3 pubmed
  4. Hernandez A, Blace N, Crary J, Serrano P, Leitges M, Libien J, et al. 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;278:40305-16 pubmed
    ..Because PKM zeta is a kinase synthesized in an autonomously active form and is necessary and sufficient for maintaining LTP, it serves as an example of a link coupling gene expression directly to synaptic plasticity. ..
  5. Kwapis J, Jarome T, Lonergan M, Helmstetter F. Protein kinase Mzeta maintains fear memory in the amygdala but not in the hippocampus. Behav Neurosci. 2009;123:844-50 pubmed publisher
    ..This suggests that PKMzeta may only maintain select forms of memory in specific brain structures and does not participate in a universal memory storage mechanism. ..
  6. Migues P, Hardt O, Wu D, Gamache K, Sacktor T, Wang Y, et al. PKMzeta maintains memories by regulating GluR2-dependent AMPA receptor trafficking. Nat Neurosci. 2010;13:630-4 pubmed publisher
    ..Together, these findings indicate that PKMzeta maintains long-term memory by regulating the trafficking of GluR2-containing AMPA receptors, the postsynaptic expression of which directly predicts memory retention. ..
  7. Serrano P, Yao Y, Sacktor T. Persistent phosphorylation by protein kinase Mzeta maintains late-phase long-term potentiation. J Neurosci. 2005;25:1979-84 pubmed
    ..An inactive scrambled version of the peptide had no effect on LTP. Thus, persistent, increased phosphorylation by PKMzeta specifically maintains the late phase of LTP. ..
  8. Marchand F, D Mello R, Yip P, Calvo M, Muller E, Pezet S, et al. Specific involvement of atypical PKC?/PKM? in spinal persistent nociceptive processing following peripheral inflammation in rat. Mol Pain. 2011;7:86 pubmed publisher
    ..These results suggest that PKC?, especially PKM? isoform, is a significant factor involved in spinal persistent nociceptive processing, specifically, the manifestation of chronic pain states following peripheral inflammation. ..
  9. Puls A, Schmidt S, Grawe F, Stabel S. Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein. Proc Natl Acad Sci U S A. 1997;94:6191-6 pubmed
    ..Taking into account the recent isolation of ZIP by others in different contexts we propose that ZIP may function as a scaffold protein linking PKC-zeta to protein tyrosine kinases and cytokine receptors. ..
  10. Parsons R, Davis M. Temporary disruption of fear-potentiated startle following PKM? inhibition in the amygdala. Nat Neurosci. 2011;14:295-6 pubmed publisher
    ..These results suggest that PKM? inhibition does not erase memory, but temporarily disrupts expression of memory. ..
  11. Vohra B, Fu M, Heuckeroth R. Protein kinase Czeta and glycogen synthase kinase-3beta control neuronal polarity in developing rodent enteric neurons, whereas SMAD specific E3 ubiquitin protein ligase 1 promotes neurite growth but does not influence polarity. J Neurosci. 2007;27:9458-68 pubmed
  12. Lefranc F, Lubicz B, Dewitte O. In vitro evidence of the role of hemoglobin during vasospasm on the modifications of the expression of PKCalpha and zeta. Int J Mol Med. 2007;20:415-9 pubmed
    ..Our results encourage the prophylactic use of specific PKC isoform antagonists associated with calcium channel blockers early after SAH to prevent cerebral vasospasm. ..
  13. Laferriere A, Pitcher M, Haldane A, Huang Y, Cornea V, Kumar N, et al. PKM? is essential for spinal plasticity underlying the maintenance of persistent pain. Mol Pain. 2011;7:99 pubmed publisher
    ..These results suggest spinal PKM? is essential for the maintenance of persistent pain by sustaining spinal nociceptive plasticity. ..
  14. Moulakakis C, Adam S, Seitzer U, Schromm A, Leitges M, Stamme C. Surfactant protein A activation of atypical protein kinase C zeta in IkappaB-alpha-dependent anti-inflammatory immune regulation. J Immunol. 2007;179:4480-91 pubmed
  15. Kim J, Cordova A, Hirayama Y, Madri J, Sumpio B. Differential effects of shear stress and cyclic strain on Sp1 phosphorylation by protein kinase Czeta modulates membrane type 1-matrix metalloproteinase in endothelial cells. Endothelium. 2008;15:33-42 pubmed publisher
  16. Lynn E, McLeod C, Gordon J, Bao J, Sack M. SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via regulation of 14-3-3 zeta and BAD in H9c2 cells. FEBS Lett. 2008;582:2857-62 pubmed publisher
    ..SIRT2 functions to moderate cellular stress-tolerance, in part, by modulating the levels of 14-3-3 zeta with the concordant control of BAD subcellular localization. ..
  17. Urbanczyk A, Junemann A, Enz R. PKC?-interacting protein ZIP3 is generated by intronic polyadenylation, and is expressed in the brain and retina of the rat. Biochem J. 2011;433:43-50 pubmed publisher
    ..In summary, we detected ZIP3-like transcripts in rat- and human-derived samples and describe the expression of ZIP3 in the rat CNS. ..
  18. Peng Y, Sigua C, Karsonovich C, Murr M. Protein kinase C-zeta (PKC-zeta) regulates Kupffer cell apoptosis during experimental sepsis. J Gastrointest Surg. 2007;11:1712-21 pubmed
    ..001). PKC-zeta plays an important role in sepsis-induced apoptosis of Kupffer cells via activation of NF-kappaB and Fas/FasL. Manipulating the response of Kupffer cells to cellular stress may have important therapeutic implications. ..
  19. Luiken J, Ouwens D, Habets D, van der Zon G, Coumans W, Schwenk R, et al. Permissive action of protein kinase C-zeta in insulin-induced CD36- and GLUT4 translocation in cardiac myocytes. J Endocrinol. 2009;201:199-209 pubmed publisher
    ..However, PKC-zeta is already fully active under basal conditions and not further activated by insulin, indicating that its role in insulin-stimulated uptake of both glucose and LCFA is permissive rather than regulatory. ..
  20. Lampugnani M, Orsenigo F, Rudini N, Maddaluno L, Boulday G, Chapon F, et al. CCM1 regulates vascular-lumen organization by inducing endothelial polarity. J Cell Sci. 2010;123:1073-80 pubmed publisher
    ..We propose that VEC, CCM1 and Rap1 form a signaling complex. In the absence of any of these proteins, AJs are dismantled, cell polarity is lost and vascular lumenal structure is severely altered. ..
  21. Siddiqi S, Mansbach C. Dietary and biliary phosphatidylcholine activates PKCζ in rat intestine. J Lipid Res. 2015;56:859-70 pubmed publisher
    ..We conclude that PKCζ on activation changes its conformation resulting in elution from its vesicle. The downstream effect of dietary PC is to activate PKCζ, resulting in greater chylomicron output by the ER. ..
  22. Diaz Meco M, Dominguez I, Sanz L, Dent P, Lozano J, Municio M, et al. zeta PKC induces phosphorylation and inactivation of I kappa B-alpha in vitro. EMBO J. 1994;13:2842-8 pubmed
    ..However, neither MKK nor MAPK is responsible for the putative I kappa B phosphorylating activity. These data provide a decisive step towards understanding the functions of zeta PKC. ..
  23. Parmentier J, Zhang C, Estes A, Schaefer S, Malik K. Essential role of PKC-zeta in normal and angiotensin II-accelerated neointimal growth after vascular injury. Am J Physiol Heart Circ Physiol. 2006;291:H1602-13 pubmed
  24. Schuette S, Fernández Fernández D, Lamla T, Rosenbrock H, Hobson S. Overexpression of Protein Kinase M? in the Hippocampus Enhances Long-Term Potentiation and Long-Term Contextual But Not Cued Fear Memory in Rats. J Neurosci. 2016;36:4313-24 pubmed publisher
    ..To our knowledge, this is the first study to combine these aspects with the result of enhanced memory for contextual fear memory and to show enhanced LTP in hippocampal slices overexpressing PKM?. ..
  25. Wang J, Meng F, Cottrell J, Sacktor T, Kass I. Metabotropic actions of the volatile anaesthetic sevoflurane increase protein kinase M synthesis and induce immediate preconditioning protection of rat hippocampal slices. J Physiol. 2012;590:4093-107 pubmed publisher
    ..This hyperpolarization delays and attenuates the hypoxic depolarization, improving the recovery of neurons following hypoxia. Thus, sevoflurane acts via a metabotropic pathway to improve recovery following hypoxia. ..
  26. Monick M, Carter A, Flaherty D, Peterson M, Hunninghake G. Protein kinase C zeta plays a central role in activation of the p42/44 mitogen-activated protein kinase by endotoxin in alveolar macrophages. J Immunol. 2000;165:4632-9 pubmed
    ..Taken as a whole, these studies suggest that LPS activates ERK kinase, in part, through activation of an atypical PKC isoform, PKC zeta. ..
  27. Wesemann D, Qin H, Kokorina N, Benveniste E. TRADD interacts with STAT1-alpha and influences interferon-gamma signaling. Nat Immunol. 2004;5:199-207 pubmed
    ..These data indicate that TRADD may be involved in IFN-gamma signaling by forming a complex with STAT1-alpha within the nucleus and regulating IFN-gamma-mediated STAT1-alpha activation. ..
  28. Hennige A, Fritsche A, Strack V, Weigert C, Mischak H, Borboni P, et al. PKC zeta enhances insulin-like growth factor 1-dependent mitogenic activity in the rat clonal beta cell line RIN 1046-38. Biochem Biophys Res Commun. 2002;290:85-90 pubmed
    ..Our data suggest that PKC zeta is involved in basal as well as IGF-1-dependent mitogenesis in RIN 1046-38 cells, while none of the PKC isoforms tested seem to be related to glucose-stimulated insulin release. ..
  29. Sajikumar S, Korte M. Metaplasticity governs compartmentalization of synaptic tagging and capture through brain-derived neurotrophic factor (BDNF) and protein kinase Mzeta (PKMzeta). Proc Natl Acad Sci U S A. 2011;108:2551-6 pubmed publisher
    ..These clusters will then prepare the synaptic network to form long-term memories. ..
  30. Li J, Gao H, Huang J, Wang P, Huang Y, Luo W, et al. PKC? interacts with STAT3 and promotes its activation in cardiomyocyte hypertrophy. J Pharmacol Sci. 2016;132:15-23 pubmed publisher
    ..In conclusion, PKC? interacts with STAT3 and promotes its activation in cardiomyocyte hypertrophy. Strategies targeting inhibition of PKC?-STAT3 signaling pathway suggest a therapeutic potential for cardiac hypertrophy. ..
  31. Kwapis J, Jarome T, Gilmartin M, Helmstetter F. Intra-amygdala infusion of the protein kinase Mzeta inhibitor ZIP disrupts foreground context fear memory. Neurobiol Learn Mem. 2012;98:148-53 pubmed publisher
  32. Wang D, Liu P, Hung H, Chen T. Both PKM? and KIBRA are closely related to reference memory but not working memory in a T-maze task in rats. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2014;200:77-82 pubmed publisher
    ..These results provide the first evidence that KIBRA as well as PKM? is closely related to reference memory but not working memory in rats. ..
  33. Oliver C, Kabitzke P, Serrano P, Egan L, Barr G, Shair H, et al. Repeated recall and PKMζ maintain fear memories in juvenile rats. Learn Mem. 2016;23:710-713 pubmed publisher
    ..These data suggest that repeated reminders and increased PKMζ maintain fear responses in juvenile animals that otherwise would not exhibit this behavior. ..
  34. Jaadane I, Chahory S, Leprêtre C, Omri B, Jonet L, Behar Cohen F, et al. The activation of the atypical PKC zeta in light-induced retinal degeneration and its involvement in L-DNase II control. J Cell Mol Med. 2015;19:1646-55 pubmed publisher
    ..These results highlight the role of PKC zeta in retinal physiology and show that this kinase can control caspase-independent pathways. ..
  35. Alam R, Hachiya N, Sakaguchi M, Kawabata S, Iwanaga S, Kitajima M, et al. cDNA cloning and characterization of mitochondrial import stimulation factor (MSF) purified from rat liver cytosol. J Biochem. 1994;116:416-25 pubmed
    ..Identification of MSF as 14-3-3 proteins establishes a novel function for this family of proteins and indicates their role as cytosolic chaperones to aid many important cellular events. ..
  36. Xia L, Wang H, Munk S, Frecker H, Goldberg H, Fantus I, et al. Reactive oxygen species, PKC-beta1, and PKC-zeta mediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells. Am J Physiol Endocrinol Metab. 2007;293:E1280-8 pubmed
    ..Thus reactive oxygen species generated by NADPH oxidase, and both PKC-beta(1) and -zeta, play important roles in high-glucose-stimulated VEGF expression and secretion by mesangial cells. ..
  37. Peng Y, Sigua C, Gallagher S, Murr M. Protein kinase C-zeta is critical in pancreatitis-induced apoptosis of Kupffer cells. J Gastrointest Surg. 2007;11:1253-61 pubmed
    ..The ability of Kupffer cells to autoregulate their stress response by upregulating their death receptor/ligand and key proapoptotic cell signaling systems warrants further investigation. ..
  38. Ryu J, Hah J, Park J, Lee W, Rampal A, Jung C. Protein kinase C-zeta phosphorylates insulin-responsive aminopeptidase in vitro at Ser-80 and Ser-91. Arch Biochem Biophys. 2002;403:71-82 pubmed
    ..These findings are consistent with the possibility that the IRAP cytoplasmic domain phosphorylation by PKC-zeta plays a key role in insulin-induced IRAP or GLUT4 recruitment in adipocytes. ..
  39. Fox T, Houck K, O Neill S, Nagarajan M, Stover T, Pomianowski P, et al. Ceramide recruits and activates protein kinase C zeta (PKC zeta) within structured membrane microdomains. J Biol Chem. 2007;282:12450-7 pubmed
    ..Taken together, these data demonstrate that structured membrane microdomains are necessary for ceramide-induced activation of PKC zeta and resultant diminished Akt activity, leading to vascular smooth muscle cell growth arrest. ..
  40. Charruyer A, Jean C, Colomba A, Jaffrezou J, Quillet Mary A, Laurent G, et al. PKCzeta protects against UV-C-induced apoptosis by inhibiting acid sphingomyelinase-dependent ceramide production. Biochem J. 2007;405:77-83 pubmed
    ..These findings may have important consequences for UV-induced carcinogenesis and resistance to phototherapy. ..
  41. Ono Y, Fujii T, Ogita K, Kikkawa U, Igarashi K, Nishizuka Y. Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties. Proc Natl Acad Sci U S A. 1989;86:3099-103 pubmed
    ..The structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from, other subspecies of protein kinase C. Perhaps, this subspecies belongs to another entity of the enzyme family. ..
  42. Li L, Zhou Y, Wang C, Zhao Y, Zhang Z, Fan D, et al. Src tyrosine kinase regulates angiotensin II-induced protein kinase Czeta activation and proliferation in vascular smooth muscle cells. Peptides. 2010;31:1159-64 pubmed publisher
    ..In conclusion, Src kinase plays an important role in AngII-elicited PKCzeta activation and the subsequent downstream signaling including ERK1/2 activation and VSMCs proliferation. ..
  43. Oehrlein S, Parker P, Herget T. Phosphorylation of GAP-43 (growth-associated protein of 43 kDa) by conventional, novel and atypical isotypes of the protein kinase C gene family: differences between oligopeptide and polypeptide phosphorylation. Biochem J. 1996;317 ( Pt 1):219-24 pubmed
    ..These results suggest that there are multiple sites of interaction between GAP-43 and PKC. ..
  44. Ishizuka T, Miura A, Kajita K, Ishizawa M, Kimura M, Huang Y, et al. Differential effect of PKC isoform on insulin- and phorbol ester-stimulated glucose uptake mechanism in rat adipocytes. IUBMB Life. 2001;51:299-304 pubmed
  45. Park J, Kim S, Chun J, Seo Y, Jeon M, Ohba M, et al. Activation of protein kinase Czeta mediates luteinizing hormone- or forskolin-induced NGFI-B expression in preovulatory granulosa cells of rat ovary. Mol Cell Endocrinol. 2007;270:79-86 pubmed
    ..Our findings demonstrate that PKCzeta, which is activated by LH or forskolin, contributes to the induction of NGFI-B in granulosa cells of preovulatory follicles. ..
  46. Cogolludo A, Moreno L, Frazziano G, Moral Sanz J, Menendez C, Castañeda J, et al. Activation of neutral sphingomyelinase is involved in acute hypoxic pulmonary vasoconstriction. Cardiovasc Res. 2009;82:296-302 pubmed publisher
    ..nSMase-derived ceramide production and the activation of PKCzeta are early and necessary events in the signalling cascade of acute HPV. ..
  47. Zhang Y, Kays J, Hodgdon K, Sacktor T, Nicol G. Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKM?. J Neurophysiol. 2012;107:315-35 pubmed publisher
    ..These results demonstrate that NGF leads to the activation of PKM? that ultimately enhances the capacity of small-diameter capsaicin-sensitive sensory neurons to fire APs through a PI3K-dependent signaling cascade. ..
  48. Levy D, Kuo A, Chang Y, Schaefer U, Kitson C, Cheung P, et al. Lysine methylation of the NF-?B subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-?B signaling. Nat Immunol. 2011;12:29-36 pubmed publisher
    ..Our findings establish a previously uncharacterized mechanism by which chromatin signaling regulates inflammation programs. ..
  49. Sato K, Iemitsu M, Aizawa K, Ajisaka R. DHEA improves impaired activation of Akt and PKC zeta/lambda-GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin-induced diabetes rats. Acta Physiol (Oxf). 2009;197:217-25 pubmed publisher
    ..Moreover, these results show that a DHEA-induced increase in muscle glucose uptake and utilization might contribute to improvement in hyperglycaemia in type 1 diabetes mellitus. ..
  50. Vinot S, Le T, Ohno S, Pawson T, Maro B, Louvet Vallee S. Asymmetric distribution of PAR proteins in the mouse embryo begins at the 8-cell stage during compaction. Dev Biol. 2005;282:307-19 pubmed
    ..Finally, they reinforce the idea that the first developmentally relevant asymmetries are set up during compaction...
  51. Gomes E, Jani S, Gundersen G. Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell. 2005;121:451-63 pubmed
    ..These results show that nuclear repositioning is an initial polarizing event in migrating cells and that the positions of the nucleus and the MTOC are established by separate regulatory pathways. ..
  52. Ehre C, Zhu Y, Abdullah L, Olsen J, Nakayama K, Nakayama K, et al. nPKCepsilon, a P2Y2-R downstream effector in regulated mucin secretion from airway goblet cells. Am J Physiol Cell Physiol. 2007;293:C1445-54 pubmed
    ..The translocation of nPKCdelta observed in activated cells is likely not related to mucin secretion but to some other aspect of goblet cell biology...