Gene Symbol: Prkcd
Description: protein kinase C, delta
Alias: Pkcd, protein kinase C delta type, nPKC-delta
Species: rat
Products:     Prkcd

Top Publications

  1. Brodie C, Blumberg P. Regulation of cell apoptosis by protein kinase c delta. Apoptosis. 2003;8:19-27 pubmed
    ..Recent findings on these aspects of the PKCdelta cascades are the major focus of this review. ..
  2. Churchill E, Szweda L. Translocation of deltaPKC to mitochondria during cardiac reperfusion enhances superoxide anion production and induces loss in mitochondrial function. Arch Biochem Biophys. 2005;439:194-9 pubmed
    ..Thus, deltaPKC represents a cytosolic redox-sensitive molecule that plays an important role in amplification of O(2)(-) production and subsequent declines in mitochondrial function during reperfusion. ..
  3. Cieslak D, Lazou A. Regulation of BAD protein by PKA, PKCdelta and phosphatases in adult rat cardiac myocytes subjected to oxidative stress. Mol Cells. 2007;24:224-31 pubmed
    ..These data suggest that, during oxidative stress-induced cardiac myocyte apoptosis, there is a caspase-dependent down-regulation of BAD protein, which seems to be regulated by coordinated action of PKA, PKCdelta and phosphatases. ..
  4. Tan M, Xu X, Ohba M, Ogawa W, Cui M. Thrombin rapidly induces protein kinase D phosphorylation, and protein kinase C delta mediates the activation. J Biol Chem. 2003;278:2824-8 pubmed
    ..Taken together, the findings of the present study demonstrate that thrombin induces activation of PKD and reveal a novel role of PKC delta in mediating thrombin-induced PKD activation in vascular smooth muscle cells. ..
  5. Raval A, Dave K, Prado R, Katz L, Busto R, Sick T, et al. Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation. J Cereb Blood Flow Metab. 2005;25:730-41 pubmed
    ..Our results support the deleterious role of deltaPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote deltaPKC translocation/cleavage. ..
  6. Lu Z, Liu D, Hornia A, Devonish W, Pagano M, Foster D. Activation of protein kinase C triggers its ubiquitination and degradation. Mol Cell Biol. 1998;18:839-45 pubmed
    ..Moreover, a kinase-dead ATP-binding mutant of PKC alpha could not be depleted by TPA treatment. These data are consistent with a suicide model whereby activation of PKC triggers its own degradation via the ubiquitin-proteasome pathway. ..
  7. Qi X, Inagaki K, Sobel R, Mochly Rosen D. Sustained pharmacological inhibition of deltaPKC protects against hypertensive encephalopathy through prevention of blood-brain barrier breakdown in rats. J Clin Invest. 2008;118:173-82 pubmed
    ..Together, these results suggest that deltaPKC plays a role in the development of hypertension-induced encephalopathy and may be a therapeutic target for the prevention of BBB disruption. ..
  8. Afeseh Ngwa H, Kanthasamy A, Anantharam V, Song C, Witte T, Houk R, et al. Vanadium induces dopaminergic neurotoxicity via protein kinase Cdelta dependent oxidative signaling mechanisms: relevance to etiopathogenesis of Parkinson's disease. Toxicol Appl Pharmacol. 2009;240:273-85 pubmed publisher
    ..Collectively, these results demonstrate that vanadium can exert neurotoxic effects in dopaminergic neuronal cells via caspase-3-dependent PKCdelta cleavage, suggesting that metal exposure may promote nigral dopaminergic degeneration. ..
  9. Kaul S, Anantharam V, Yang Y, Choi C, Kanthasamy A, Kanthasamy A. Tyrosine phosphorylation regulates the proteolytic activation of protein kinase Cdelta in dopaminergic neuronal cells. J Biol Chem. 2005;280:28721-30 pubmed
    ..To our knowledge, these data demonstrate for the first time that phosphorylation of Tyr-311 on PKCdelta can regulate the proteolytic activation and proapoptotic function of the kinase in dopaminergic neuronal cells. ..

More Information


  1. Murriel C, Churchill E, Inagaki K, Szweda L, Mochly Rosen D. Protein kinase Cdelta activation induces apoptosis in response to cardiac ischemia and reperfusion damage: a mechanism involving BAD and the mitochondria. J Biol Chem. 2004;279:47985-91 pubmed
    ..Our data suggest that PKCdelta activation has a critical proapoptotic role in cardiac responses following ischemia and reperfusion. ..
  2. Tapia J, Bragado M, Garcia Marin L, Jensen R. Cholecystokinin-stimulated tyrosine phosphorylation of PKC-delta in pancreatic acinar cells is regulated bidirectionally by PKC activation. Biochim Biophys Acta. 2002;1593:99-113 pubmed
    ..Therefore, CCK activates both stimulatory and inhibitory PKC cascades regulating PKC-delta TYR-P and, hence, likely plays an important role in regulating PKC-delta degradation and cellular abundance. ..
  3. Carvour M, Song C, Kaul S, Anantharam V, Kanthasamy A, Kanthasamy A. Chronic low-dose oxidative stress induces caspase-3-dependent PKCdelta proteolytic activation and apoptosis in a cell culture model of dopaminergic neurodegeneration. Ann N Y Acad Sci. 2008;1139:197-205 pubmed publisher
  4. Zhang D, Kanthasamy A, Yang Y, Anantharam V, Kanthasamy A. Protein kinase C delta negatively regulates tyrosine hydroxylase activity and dopamine synthesis by enhancing protein phosphatase-2A activity in dopaminergic neurons. J Neurosci. 2007;27:5349-62 pubmed
    ..Collectively, these results suggest that PKCdelta phosphorylates PP2Ac to enhance its activity and thereby reduces TH-ser40 phosphorylation and TH activity and ultimately dopamine synthesis. ..
  5. Nguyen T, Ogbi M, Johnson J. Delta protein kinase C interacts with the d subunit of the F1F0 ATPase in neonatal cardiac myocytes exposed to hypoxia or phorbol ester. Implications for F1F0 ATPase regulation. J Biol Chem. 2008;283:29831-40 pubmed publisher
    ..Our results suggest a novel regulation of the F(1)F(0) ATPase by the delta protein kinase C isozyme. ..
  6. Kaul S, Anantharam V, Kanthasamy A, Kanthasamy A. Wild-type alpha-synuclein interacts with pro-apoptotic proteins PKCdelta and BAD to protect dopaminergic neuronal cells against MPP+-induced apoptotic cell death. Brain Res Mol Brain Res. 2005;139:137-52 pubmed
    ..Together, our results demonstrate that wild-type alpha-synuclein interacts with the pro-apoptotic molecules BAD and PKCdelta to protect dopaminergic neuronal cells against neurotoxic insults. ..
  7. Ryer E, Sakakibara K, Wang C, Sarkar D, Fisher P, Faries P, et al. Protein kinase C delta induces apoptosis of vascular smooth muscle cells through induction of the tumor suppressor p53 by both p38-dependent and p38-independent mechanisms. J Biol Chem. 2005;280:35310-7 pubmed
    ..Together, our data suggest that SMC apoptosis proceeds through a pathway that involves PKCdelta, the intermediary p38 MAPK, and the downstream target tumor suppressor p53. ..
  8. Gao X, Zhang H, Takahashi T, Hsieh J, Liao J, Steinberg G, et al. The Akt signaling pathway contributes to postconditioning's protection against stroke; the protection is associated with the MAPK and PKC pathways. J Neurochem. 2008;105:943-55 pubmed publisher
  9. Saito S, Frank G, Mifune M, Ohba M, Utsunomiya H, Motley E, et al. Ligand-independent trans-activation of the platelet-derived growth factor receptor by reactive oxygen species requires protein kinase C-delta and c-Src. J Biol Chem. 2002;277:44695-700 pubmed
  10. Jung S, Kim O, Kang H, Jang D, Min B, Yu F. Protein kinase C?/? inhibitor Gö6976 promotes PC12 cell adhesion and spreading through membrane recruitment and activation of protein kinase C?. Exp Cell Res. 2013;319:153-60 pubmed publisher
    ..In addition, the activation of Rac1 and Cdc42 by human laminin-2-integrin-dependent activation of PKC?/FAK signaling mediates cell spreading and lamellipodia formation in PC12 cells. ..
  11. Pauken C, Capco D. The expression and stage-specific localization of protein kinase C isotypes during mouse preimplantation development. Dev Biol. 2000;223:411-21 pubmed
    ..Two isotypes have a stage-dependent nuclear localization. In addition, within each blastomere PKC isotypes occupy different subcellular locations in a stage-dependent fashion. ..
  12. Wiedemann S, Wessela T, Schwarz K, Joachim D, Jercke M, Strasser R, et al. Inhibition of anti-apoptotic signals by Wortmannin induces apoptosis in the remote myocardium after LAD ligation: evidence for a protein kinase C-?-dependent pathway. Mol Cell Biochem. 2013;372:275-83 pubmed publisher
    ..This gives evidence of a bi-directional crosstalk of pro- and anti-apoptotic signals after infarction. ..
  13. Fordjour A, Harrington E. PKCdelta influences p190 phosphorylation and activity: events independent of PKCdelta-mediated regulation of endothelial cell stress fiber and focal adhesion formation and barrier function. Biochim Biophys Acta. 2009;1790:1179-90 pubmed publisher
    ..Our findings suggest that while PKCdelta can regulate p190 activity, possibly at the FF and/or GTPase domains, the effect of PKCdelta inhibition on SF and FA and barrier dysfunction occurs through a pathway independent of p190. ..
  14. Zeng Z, Li Y, Jiao Z, Yao J, Xue Y. The cross talk between cGMP signal pathway and PKC in pulmonary endothelial cell angiogenesis. Int J Mol Sci. 2014;15:10185-98 pubmed publisher
    ..Taken together, these data suggest that ERK phosphorylation mediates the proliferation of pulmonary vascular endothelial cells, and PKC kinases have a permissive action in this process. ..
  15. Braun M, LaRosée P, Simonis G, Borst M, Strasser R. Regulation of protein kinase C isozymes in volume overload cardiac hypertrophy. Mol Cell Biochem. 2004;262:135-43 pubmed
    ..This study characterizes in the left and right ventricle a differential regulation of the dominant PKC-isozymes in volume-overload cardiac hypertrophy both at the protein and at the mRNA-level. ..
  16. Qi X, Disatnik M, Shen N, Sobel R, Mochly Rosen D. Aberrant mitochondrial fission in neurons induced by protein kinase C{delta} under oxidative stress conditions in vivo. Mol Biol Cell. 2011;22:256-65 pubmed publisher
    ..Our study suggests that PKC? activation dysregulates the mitochondrial fission machinery and induces aberrant mitochondrial fission, thus contributing to neurological pathology. ..
  17. Renault Mihara F, Beuvon F, Iturrioz X, Canton B, De Bouard S, Leonard N, et al. Phosphoprotein enriched in astrocytes-15 kDa expression inhibits astrocyte migration by a protein kinase C delta-dependent mechanism. Mol Biol Cell. 2006;17:5141-52 pubmed
    ..Together, these data reveal a new function for PEA-15 in the inhibitory control of astrocyte motility through a PKC delta-dependent pathway involving the constitutive expression of a catalytic fragment of PKC delta. ..
  18. Okhrimenko H, Lu W, Xiang C, Ju D, Blumberg P, Gomel R, et al. Roles of tyrosine phosphorylation and cleavage of protein kinase Cdelta in its protective effect against tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis. J Biol Chem. 2005;280:23643-52 pubmed
    ..Our results indicate that PKCdelta protects glioma cells from the apoptosis induced by TRAIL and implicate the phosphorylation of PKCdelta on tyrosine 155 and its cleavage as essential factors in the anti-apoptotic effect of PKCdelta. ..
  19. Sumandea M, Rybin V, Hinken A, Wang C, Kobayashi T, Harleton E, et al. Tyrosine phosphorylation modifies protein kinase C delta-dependent phosphorylation of cardiac troponin I. J Biol Chem. 2008;283:22680-9 pubmed publisher
  20. Chintalgattu V, Katwa L. Role of protein kinase C-delta in angiotensin II induced cardiac fibrosis. Biochem Biophys Res Commun. 2009;386:612-6 pubmed publisher
    ..This increase in cardiac collagen expression was abrogated by rottlerin treatment. In conclusion, both in vitro and in vivo data strongly suggest a role for PKC-delta in AngII induced cardiac fibrosis. ..
  21. Shimohata T, Zhao H, Sung J, Sun G, Mochly Rosen D, Steinberg G. Suppression of deltaPKC activation after focal cerebral ischemia contributes to the protective effect of hypothermia. J Cereb Blood Flow Metab. 2007;27:1463-75 pubmed
    ..Both cytochrome c release and deltaPKC translocation were blocked by hypothermia. In conclusion, hypothermia protects against ischemic damage in part by suppressing deltaPKC activation after stroke. ..
  22. Bull N, Wood J, Osborne N, Barnett N. Protein kinase C-mediated modulation of glutamate transporter activity in rat retina. Curr Eye Res. 2007;32:123-31 pubmed
    ..The current results suggest that specific PKC inhibitors are quantitatively similar in reducing the uptake of glutamate into retinal neurons and Müller cells. ..
  23. Morrish B, Rumsby M. The 5' untranslated region of protein kinase Cdelta directs translation by an internal ribosome entry segment that is most active in densely growing cells and during apoptosis. Mol Cell Biol. 2002;22:6089-99 pubmed
    ..Our studies suggest a mechanism whereby PKCdelta synthesis can be maintained under these conditions when cap-dependent translation is inhibited. ..
  24. Cui G, Gao X, Qi S, Gillani A, Gao L, Shen X, et al. The action of thrombin in intracerebral hemorrhage induced brain damage is mediated via PKC?/PKC? signaling. Brain Res. 2011;1398:86-93 pubmed publisher
    ..We conclude that both PKC? and PKC? play important roles in ICH and TM-induced brain injury, and dihydrochloride (H7) can attenuate brain damage after ICH. ..
  25. Thrower E, Osgood S, Shugrue C, Kolodecik T, Chaudhuri A, Reeve J, et al. The novel protein kinase C isoforms -delta and -epsilon modulate caerulein-induced zymogen activation in pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1344-53 pubmed publisher
    ..These results indicate that PKC-delta and -epsilon isoforms translocate to specific acinar cell compartments and modulate zymogen activation. ..
  26. Tokunaga C, Kuroda S, Tatematsu K, Nakagawa N, Ono Y, Kikkawa U. Molecular cloning and characterization of a novel protein kinase C-interacting protein with structural motifs related to RBCC family proteins. Biochem Biophys Res Commun. 1998;244:353-9 pubmed
    ..These results suggest that RBCK1 protein might be a transcription factor that has a role in the signaling pathway through PKC. ..
  27. Frank G, Saito S, Motley E, Sasaki T, Ohba M, Kuroki T, et al. Requirement of Ca(2+) and PKCdelta for Janus kinase 2 activation by angiotensin II: involvement of PYK2. Mol Endocrinol. 2002;16:367-77 pubmed
    ..These data provide a new mechanistic insight by which the hormone AngII exerts its cytokine-like actions in mediating vascular remodeling. ..
  28. Yun N, Lee S. Activation of protein kinase C delta reduces hepatocellular damage in ischemic preconditioned rat liver. J Surg Res. 2013;185:869-76 pubmed publisher
    ..Our findings suggest that IPC protects against I/R-induced hepatic injury through activation of PKC-?. ..
  29. Calvert V, Collantes R, Elariny H, Afendy A, Baranova A, Mendoza M, et al. A systems biology approach to the pathogenesis of obesity-related nonalcoholic fatty liver disease using reverse phase protein microarrays for multiplexed cell signaling analysis. Hepatology. 2007;46:166-72 pubmed
    ..These findings provide evidence for the role of omental fat in the pathogenesis, and potentially, the progression of NAFLD. ..
  30. Kurkinen K, Keinanen R, Karhu R, Koistinaho J. Genomic structure and chromosomal localization of the rat protein kinase Cdelta-gene. Gene. 2000;242:115-23 pubmed
    ..The PKCdelta gene is localized at the rat chromosome 19p14. The cloned gene will help to elucidate the role of PKCdelta in growth, differentiation and death of mammalian cells. ..
  31. Murakami M, Horowitz A, Tang S, Ware J, Simons M. Protein kinase C (PKC) delta regulates PKCalpha activity in a Syndecan-4-dependent manner. J Biol Chem. 2002;277:20367-71 pubmed
    ..The reduced PKCalpha activity then leads to impaired endothelial cell function. We conclude that PKCdelta regulates PKCalpha activity in a syndecan-4-dependent manner. ..
  32. Stahelin R, Digman M, Medkova M, Ananthanarayanan B, Melowic H, Rafter J, et al. Diacylglycerol-induced membrane targeting and activation of protein kinase Cepsilon: mechanistic differences between protein kinases Cdelta and Cepsilon. J Biol Chem. 2005;280:19784-93 pubmed
    ..Collectively, these results provide new insight into the differential activation mechanisms of PKCdelta and PKCepsilon based on different structural and functional properties of their C1 domains. ..
  33. Kubo Murai M, Hazeki K, Sukenobu N, Yoshikawa K, Nigorikawa K, Inoue K, et al. Protein kinase Cdelta binds TIRAP/Mal to participate in TLR signaling. Mol Immunol. 2007;44:2257-64 pubmed
    ..TLR2- and TLR4-mediated phosphorylation of p38 MAPK, IKK, and IkappaB in RAW264.7 cells were abolished by depletion of PKCdelta. These results suggest that PKCdelta binding to TIRAP/Mal promotes TLR signaling events. ..
  34. Kajimoto T, Shirai Y, Sakai N, Yamamoto T, Matsuzaki H, Kikkawa U, et al. Ceramide-induced apoptosis by translocation, phosphorylation, and activation of protein kinase Cdelta in the Golgi complex. J Biol Chem. 2004;279:12668-76 pubmed
    ..We demonstrate here that the targeting mechanism of PKCdelta, dual regulation of both its activation and translocation to the Golgi complex, is critical for the ceramide-induced apoptotic event. ..
  35. Pula G, Schuh K, Nakayama K, Nakayama K, Walter U, Poole A. PKCdelta regulates collagen-induced platelet aggregation through inhibition of VASP-mediated filopodia formation. Blood. 2006;108:4035-44 pubmed
    ..PKCdelta is therefore a critical negative regulator of filopodia, and hence platelet aggregation, through a functional interaction with the actin organizer VASP. ..
  36. Markou T, Yong C, Sugden P, Clerk A. Regulation of protein kinase C delta by phorbol ester, endothelin-1, and platelet-derived growth factor in cardiac myocytes. J Biol Chem. 2006;281:8321-31 pubmed
    ..We concluded that, with this physiological agonist, PKCdelta becomes activated in the particulate fraction but retains activity following its retrotranslocation, presumably to phosphorylate substrates elsewhere. ..
  37. Matassa A, Kalkofen R, Carpenter L, Biden T, Reyland M. Inhibition of PKCalpha induces a PKCdelta-dependent apoptotic program in salivary epithelial cells. Cell Death Differ. 2003;10:269-77 pubmed
    ..These findings indicate that PKCalpha functions as a survival factor in salivary epithelial cells, while PKCdelta functions to regulate entry into the apoptotic pathway. ..
  38. Adwan T, Ohm A, Jones D, Humphries M, Reyland M. Regulated binding of importin-? to protein kinase C? in response to apoptotic signals facilitates nuclear import. J Biol Chem. 2011;286:35716-24 pubmed publisher
    ..Taken together, this study establishes a novel mechanism that retains PKC? in the cytoplasm of resting cells and regulates its nuclear import in response to apoptotic stimuli. ..
  39. Cunningham R, Giuffrida A, Roberts J. Androgens induce dopaminergic neurotoxicity via caspase-3-dependent activation of protein kinase Cdelta. Endocrinology. 2009;150:5539-48 pubmed publisher
    ..These results support a neurotoxic consequence of testosterone on dopaminergic neurons and may provide insight into the gender bias found in PD. ..
  40. Zara S, Falconi M, Rapino M, Zago M, Orsini G, Mazzotti G, et al. pPKC? activates SC35 splicing factor during H9c2 myoblastic differentiation. Histol Histopathol. 2011;26:59-69 pubmed publisher
    ..Furthermore, this co-localization represents a crucial event resulting in downstream changes in transcription of components which determine the morphological modifications related to cardiomyoblast differentiated phenotype. ..
  41. Chichger H, Vang A, O Connell K, Zhang P, Mende U, Harrington E, et al. PKC δ and βII regulate angiotensin II-mediated fibrosis through p38: a mechanism of RV fibrosis in pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2015;308:L827-36 pubmed publisher
  42. Pan T, Neo K, Hu L, Yong Q, Bian J. H2S preconditioning-induced PKC activation regulates intracellular calcium handling in rat cardiomyocytes. Am J Physiol Cell Physiol. 2008;294:C169-77 pubmed
    ..Such PKC activation, in turn, protects the heart against ischemia-reperfusion insults at least partly by ameliorating intracellular Ca(2+) handling. ..
  43. Kilpatrick L, Sun S, Li H, Vary T, Korchak H. Regulation of TNF-induced oxygen radical production in human neutrophils: role of delta-PKC. J Leukoc Biol. 2010;87:153-64 pubmed publisher activates p47phox by serine phosphorylation or indirectly through control of ERK recruitment to p47phox. ..
  44. Lin C, Lee I, Chi P, Hsieh H, Cheng S, Hsiao L, et al. C-Src/Jak2/PDGFR/PKC?-dependent MMP-9 induction is required for thrombin-stimulated rat brain astrocytes migration. Mol Neurobiol. 2014;49:658-72 pubmed publisher
    ..These results concluded that in RBA-1 cells, thrombin activated a c-Src/Jak2/PDGFR/PI3K/Akt/PKC? pathway, which in turn triggered ATF2 and NF-?B activation and ultimately induced MMP-9 expression associated with cell migration. ..
  45. Kato K, Yamanouchi D, Esbona K, Kamiya K, Zhang F, Kent K, et al. Caspase-mediated protein kinase C-delta cleavage is necessary for apoptosis of vascular smooth muscle cells. Am J Physiol Heart Circ Physiol. 2009;297:H2253-61 pubmed publisher
    ..Taken together, our data suggest that caspase-3-mediated PKC-delta cleavage underlies SMC apoptosis induced by oxidative stress, and that PKC-delta acts both upstream and downstream of caspase-3. ..
  46. Klinger J, Murray J, Casserly B, Alvarez D, King J, An S, et al. Rottlerin causes pulmonary edema in vivo: a possible role for PKCdelta. J Appl Physiol (1985). 2007;103:2084-94 pubmed
    ..Taken together, rottlerin increases barrier dysfunction in pulmonary endothelial cell monolayers and causes pulmonary edema in rats; results suggestive of an important role for PKCdelta in maintaining lung endothelial barrier function. ..
  47. Gong J, Holewinski R, Van Eyk J, Steinberg S. A novel phosphorylation site at Ser130 adjacent to the pseudosubstrate domain contributes to the activation of protein kinase C-δ. Biochem J. 2016;473:311-20 pubmed publisher
  48. Zhang Y, Li H, Pu Y, Gong S, Liu C, Jiang X, et al. Melatonin-mediated inhibition of Purkinje neuron P-type Ca²⁺ channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3-kinase-dependent protein kinase C delta pathway. J Pineal Res. 2015;58:321-34 pubmed publisher
    ..This likely contributes to its physiological functions, including spontaneous firing of cerebellar Purkinje neurons. ..
  49. Asaithambi A, Kanthasamy A, Saminathan H, Anantharam V, Kanthasamy A. Protein kinase D1 (PKD1) activation mediates a compensatory protective response during early stages of oxidative stress-induced neuronal degeneration. Mol Neurodegener. 2011;6:43 pubmed publisher
    ..Our results suggest that positive modulation of the PKD1-mediated compensatory protective mechanism against oxidative damage in dopaminergic neurons may provide novel neuroprotective strategies for treatment of PD. ..
  50. Kuriyama M, Taniguchi T, Shirai Y, Sasaki A, Yoshimura A, Saito N. Activation and translocation of PKCdelta is necessary for VEGF-induced ERK activation through KDR in HEK293T cells. Biochem Biophys Res Commun. 2004;325:843-51 pubmed
    ..These results indicate that PKCdelta is involved in VEGF-KDR-induced ERK activation via C1B domain. ..
  51. Hlaváčková M, Kožichová K, Neckar J, Kolar F, Musters R, Novak F, et al. Up-regulation and redistribution of protein kinase C-? in chronically hypoxic heart. Mol Cell Biochem. 2010;345:271-82 pubmed publisher
    ..The inhibitory effects of rottlerin on PKC-? subcellular redistribution and cardioprotection (as shown previously) support the view that this isoform plays a role in the mechanism of CIH-induced ischemic tolerance. ..
  52. Di Giacomo V, Rapino M, Sancilio S, Patruno A, Zara S, Di Pietro R, et al. PKC-? signalling pathway is involved in H9c2 cells differentiation. Differentiation. 2010;80:204-12 pubmed publisher
  53. Chang J, Wendt T, Qu W, Kong L, Zou Y, Schmidt A, et al. Oxygen deprivation triggers upregulation of early growth response-1 by the receptor for advanced glycation end products. Circ Res. 2008;102:905-13 pubmed publisher
    ..These findings identify RAGE as a master regulator of tissue stress elicited by hypoxia and highlight this receptor as a central therapeutic target to suppress the tissue injury-provoking effects of oxygen deprivation. ..
  54. Greene M, Morrice N, Garofalo R, Roth R. Modulation of human insulin receptor substrate-1 tyrosine phosphorylation by protein kinase Cdelta. Biochem J. 2004;378:105-16 pubmed
    ..These results indicate that PKCdelta modulates the ability of the insulin receptor to tyrosine-phosphorylate IRS-1 by direct phosphorylation of the IRS-1 molecule. ..
  55. Berna M, Hoffmann K, Tapia J, Thill M, Pace A, Mantey S, et al. CCK causes PKD1 activation in pancreatic acini by signaling through PKC-delta and PKC-independent pathways. Biochim Biophys Acta. 2007;1773:483-501 pubmed
    ..CCK stimulated translocation of total and phosphorylated PKD1 to the membrane. These results demonstrate that CCK(A) receptor activation leads to PKD activation by signaling through PKC-dependent and PKC-independent pathways. ..
  56. Snetkov V, Thomas G, Teague B, Leach R, Shaifta Y, Knock G, et al. Low concentrations of sphingosylphosphorylcholine enhance pulmonary artery vasoreactivity: the role of protein kinase C delta and Ca2+ entry. Hypertension. 2008;51:239-45 pubmed
    ..This has implications for the physiological role of SPC, especially in cardiovascular disease, where SPC is reported to be elevated. ..
  57. Ueyama T, Ren Y, Ohmori S, Sakai K, Tamaki N, Saito N. cDNA cloning of an alternative splicing variant of protein kinase C delta (PKC deltaIII), a new truncated form of PKCdelta, in rats. Biochem Biophys Res Commun. 2000;269:557-63 pubmed
  58. Ha H, Yu M, Choi Y, Lee H. Activation of protein kinase c-delta and c-epsilon by oxidative stress in early diabetic rat kidney. Am J Kidney Dis. 2001;38:S204-7 pubmed
    ..These data suggest that PKC-delta and PKC-epsilon are sensitively activated by hyperglycemia-induced oxidative stress in diabetic rat kidney. ..
  59. Sugden M, Langdown M. Possible involvement of PKC isoforms in signalling placental apoptosis in intrauterine growth retardation. Mol Cell Endocrinol. 2001;185:119-26 pubmed
  60. Thrower E, Wang J, Cheriyan S, Lugea A, Kolodecik T, Yuan J, et al. Protein kinase C delta-mediated processes in cholecystokinin-8-stimulated pancreatic acini. Pancreas. 2009;38:930-5 pubmed publisher
    ..We could not confirm that it mediates amylase release but corroborated its role in the early stages of acute pancreatitis. ..
  61. Ginnan R, Jourd heuil F, Guikema B, Simons M, Singer H, JOURD HEUIL D. NADPH oxidase 4 is required for interleukin-1β-mediated activation of protein kinase Cδ and downstream activation of c-jun N-terminal kinase signaling in smooth muscle. Free Radic Biol Med. 2013;54:125-34 pubmed publisher
    ..Our study positions PKCδ as an important redox-sensitive mediator of IL-1β-dependent signaling and downstream activation of inflammatory mediators in VSM cells. ..
  62. Suh K, Tatunchak T, Crutchley J, Edwards L, Marin K, Yuspa S. Genomic structure and promoter analysis of PKC-delta. Genomics. 2003;82:57-67 pubmed
    ..This TNF-alpha-mediated upregulation of PKC-delta is repressed in keratinocytes that are preinfected with IkappaB superrepressor adenovirus, suggesting that NFkappaB is involved directly in PKC-delta expression. ..
  63. Ono Y, Fujii T, Ogita K, Kikkawa U, Igarashi K, Nishizuka Y. Identification of three additional members of rat protein kinase C family: delta-, epsilon- and zeta-subspecies. FEBS Lett. 1987;226:125-8 pubmed
    ..The diverse heterogeneity of the enzyme seems to be an important factor in determining the mode of response of many tissues and cell types to a variety of external stimuli. ..
  64. Gaudreault N, Perrin R, Guo M, Clanton C, Wu M, Yuan S. Counter regulatory effects of PKCbetaII and PKCdelta on coronary endothelial permeability. Arterioscler Thromb Vasc Biol. 2008;28:1527-33 pubmed publisher
    ..Imbalanced PKC(betaII)/PKCdelta expression and activity may contribute to endothelial hyperpermeability and coronary dysfunction in diabetes. ..
  65. Gao Y, Zou J, Geng S, Zheng J, Yang J. Role of protein kinase C in the activation of store-operated Ca(2+) entry in airway smooth muscle cells. J Huazhong Univ Sci Technolog Med Sci. 2012;32:303-310 pubmed publisher
    ..These results identified PKC? as an essential PKC isoform involved in the activation of SOCE, and confirmed that PKC regulates the function of ASMCs in a SOCE-dependent manner. ..
  66. Rybin V, Guo J, Harleton E, Feinmark S, Steinberg S. Regulatory autophosphorylation sites on protein kinase C-delta at threonine-141 and threonine-295. Biochemistry. 2009;48:4642-51 pubmed publisher
    ..Collectively, these studies identify novel regulatory autophosphorylations on PKCdelta that serve as markers and regulators of PKCdelta activity. ..
  67. Strasser D, Neumann K, Bergmann H, Marakalala M, Guler R, Rojowska A, et al. Syk kinase-coupled C-type lectin receptors engage protein kinase C-σ to elicit Card9 adaptor-mediated innate immunity. Immunity. 2012;36:32-42 pubmed publisher
    ..b>Prkcd(-/-) dendritic cells, but not those lacking PKCα, PKCβ, or PKCθ, were defective in innate responses to ..
  68. 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...
  69. Harrington E, Shannon C, Morin N, Rowlett H, Murphy C, Lu Q. PKCdelta regulates endothelial basal barrier function through modulation of RhoA GTPase activity. Exp Cell Res. 2005;308:407-21 pubmed
    ..Thus, PKCdelta may regulate basal endothelial barrier function by stabilizing microfilaments and focal contacts by regulating RhoA GTPase activity through upstream modulators, p190RhoGAP and p120RasGAP. ..
  70. Hamplova B, Novak F, Kolar F, Novakova O. Transient upregulation of protein kinase C in pressure-overloaded neonatal rat myocardium. Physiol Res. 2010;59:25-33 pubmed
    ..It is concluded that PKCalpha, PKCdelta and PKCepsilon undergo transient upregulation associated with the accelerated cardiac growth induced by pressure overload imposed in the very early postnatal period. ..
  71. Karagulova G, Yue Y, Moreyra A, Boutjdir M, Korichneva I. Protective role of intracellular zinc in myocardial ischemia/reperfusion is associated with preservation of protein kinase C isoforms. J Pharmacol Exp Ther. 2007;321:517-25 pubmed
    ..The data support the potential clinical use of zinc ionophores in the settings of acute redox stress in the heart. ..
  72. Clavijo C, Chen J, Kim K, Reyland M, Ann D. Protein kinase Cdelta-dependent and -independent signaling in genotoxic response to treatment of desferroxamine, a hypoxia-mimetic agent. Am J Physiol Cell Physiol. 2007;292:C2150-60 pubmed
    ..In summary, these findings suggest that the activation of a PKCdelta-mediated signaling network is one of the critical contributing factors involved in fine-tuning of the DNA damage response to DFO treatment. ..
  73. Hsieh H, Wang H, Wu C, Jou M, Yen M, Parker P, et al. BK-induced COX-2 expression via PKC-delta-dependent activation of p42/p44 MAPK and NF-kappaB in astrocytes. Cell Signal. 2007;19:330-40 pubmed
    ..Understanding the regulation of COX-2 expression and PGE(2) release induced by BK in astrocytes might provide a new therapeutic strategy of brain injury and inflammatory diseases. ..
  74. Melling C, Thorp D, Milne K, Noble E. Myocardial Hsp70 phosphorylation and PKC-mediated cardioprotection following exercise. Cell Stress Chaperones. 2009;14:141-50 pubmed publisher
    ..However, exercise-induced phosphorylation of Hsp70 does not appear to be a mechanism by which PKC induces this cardioprotective effect. ..
  75. Hunter J, Kostyak J, Novotny J, Simpson A, Korzick D. Estrogen deficiency decreases ischemic tolerance in the aged rat heart: Roles of PKCdelta, PKCepsilon, Akt, and GSK3beta. Am J Physiol Regul Integr Comp Physiol. 2007;292:R800-9 pubmed
  76. Kokorovic A, Cheung G, Breen D, Chari M, Lam C, Lam T. Duodenal mucosal protein kinase C-? regulates glucose production in rats. Gastroenterology. 2011;141:1720-7 pubmed publisher
    ..Molecular and pharmacologic inhibition of duodenal mucosal PKC-? negated the ability of duodenal OAG and lipids to reduce glucose production. In the duodenal mucosa, PKC-? regulates glucose homeostasis. ..
  77. Lv P, Miao S, Shu Y, Dong L, Liu G, Xie X, et al. Phosphorylation of smooth muscle 22? facilitates angiotensin II-induced ROS production via activation of the PKC?-P47phox axis through release of PKC? and actin dynamics and is associated with hypertrophy and hyperplasia of vascular smooth muscle cel. Circ Res. 2012;111:697-707 pubmed publisher
    ..However, the mechanisms by which SM22? controls ROS production have not been characterized...
  78. Dave K, Bhattacharya S, Saul I, DeFazio R, Dezfulian C, Lin H, et al. Activation of protein kinase C delta following cerebral ischemia leads to release of cytochrome C from the mitochondria via bad pathway. PLoS ONE. 2011;6:e22057 pubmed publisher
  79. Horovitz Fried M, Sampson S. Involvement of PKCalpha in insulin-induced PKCdelta expression: Importance of SP-1 and NFkappaB transcription factors. Biochem Biophys Res Commun. 2007;352:78-83 pubmed
    ..Inhibition of PKCdelta reduced IkappaBalpha phosphorylation as well as NFkappaB activation. Thus, PKCalpha regulates insulin-induced PKCdelta expression levels and this regulation involves activation of SP-1 and NFkappaB. ..
  80. Li X, Pabla N, Wei Q, Dong G, Messing R, Wang C, et al. PKC-delta promotes renal tubular cell apoptosis associated with proteinuria. J Am Soc Nephrol. 2010;21:1115-24 pubmed publisher
    ..Taken together, these results suggest that activation of PKC-delta promotes tubular cell injury and death during albuminuria, broadening our understanding of the pathogenesis of progressive proteinuric kidney diseases. ..
  81. Hanrott K, Gudmunsen L, O Neill M, Wonnacott S. 6-hydroxydopamine-induced apoptosis is mediated via extracellular auto-oxidation and caspase 3-dependent activation of protein kinase Cdelta. J Biol Chem. 2006;281:5373-82 pubmed
  82. Iyoda T, Zhang F, Sun L, Hao F, Schmitz Peiffer C, Xu X, et al. Lysophosphatidic acid induces early growth response-1 (Egr-1) protein expression via protein kinase C?-regulated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation in vascular smooth muscle cells. J Biol Chem. 2012;287:22635-42 pubmed publisher
    ..This study provides the first evidence that PKC? mediates ERK and JNK activation in the LPA signaling pathway and that this pathway is required for LPA-induced gene regulation as evidenced by Egr-1 expression. ..
  83. Wrede C, Dickson L, Lingohr M, Briaud I, Rhodes C. Fatty acid and phorbol ester-mediated interference of mitogenic signaling via novel protein kinase C isoforms in pancreatic beta-cells (INS-1). J Mol Endocrinol. 2003;30:271-86 pubmed
  84. Han J, Kim J, Lee B, Lee S, Kim Y, Jung Y, et al. Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells. J Biol Chem. 2002;277:8290-7 pubmed
    ..These results suggest that PKC delta-dependent direct phosphorylation plays an important role in the regulation of PLD2 activity in PC12 cells. ..
  85. Anantharam V, Lehrmann E, Kanthasamy A, Yang Y, Banerjee P, Becker K, et al. Microarray analysis of oxidative stress regulated genes in mesencephalic dopaminergic neuronal cells: relevance to oxidative damage in Parkinson's disease. Neurochem Int. 2007;50:834-47 pubmed
    ..Utilizing this in vitro model to identify novel oxidative stress-regulated genes may be useful in unraveling the molecular mechanisms underlying dopaminergic degeneration in Parkinson's disease. ..
  86. Blesson C, Chinnathambi V, Hankins G, Yallampalli C, Sathishkumar K. Prenatal testosterone exposure induces hypertension in adult females via androgen receptor-dependent protein kinase Cδ-mediated mechanism. Hypertension. 2015;65:683-690 pubmed publisher
    ..Our studies identified a novel androgen-mediated mechanism for the control of PKCδ expression via transcriptional regulation that controls vasoconstriction and blood pressure. ..
  87. Coutinho I, Pereira C, Pereira G, Gon alves J, C rte Real M, Saraiva L. Distinct regulation of p53-mediated apoptosis by protein kinase C?, ?, ? and ?: Evidence in yeast for transcription-dependent and -independent p53 apoptotic mechanisms. Exp Cell Res. 2011;317:1147-58 pubmed publisher
    ..Finally, it underscores a major role of PKC? and ? as positive regulators of p53-mediated apoptosis, and therefore as promising therapeutic targets in cancer...
  88. Rybin V, Guo J, Gertsberg Z, Feinmark S, Steinberg S. Phorbol 12-myristate 13-acetate-dependent protein kinase C delta-Tyr311 phosphorylation in cardiomyocyte caveolae. J Biol Chem. 2008;283:17777-88 pubmed publisher
    ..Collectively, these results identify stimulus-specific PKCdelta localization and tyrosine phosphorylation mechanisms that could be targeted for therapeutic advantage. ..
  89. Nguyen T, Ogbi M, Yu Q, Johnson J. Attenuation of the hypoxia-induced protein kinase Cdelta interaction with the 'd' subunit of F1Fo-ATP synthase in neonatal cardiac myocytes: implications for energy preservation and survival. Biochem J. 2010;429:335-45 pubmed publisher
    ..Our studies provide the first evidence that disruption of the PKCdelta-dF1Fo interaction using cell-permeant mitochondrial-targeted peptides attenuates cardiac injury resulting from prolonged oxygen deprivation...
  90. Ishida K, Matsumoto T, Taguchi K, Kamata K, Kobayashi T. Protein kinase C delta contributes to increase in EP3 agonist-induced contraction in mesenteric arteries from type 2 diabetic Goto-Kakizaki rats. Pflugers Arch. 2012;463:593-602 pubmed publisher
    ..Alterations in EP3 receptor-mediated vasocontraction may be important factors in the pathophysiological influences over arterial tone that are present in diabetic states. ..
  91. Talior I, Tennenbaum T, Kuroki T, Eldar Finkelman H. PKC-delta-dependent activation of oxidative stress in adipocytes of obese and insulin-resistant mice: role for NADPH oxidase. Am J Physiol Endocrinol Metab. 2005;288:E405-11 pubmed
    ..Taken together, these results suggest that PKC-delta is responsible for elevated intracellular ROS production in HF adipocytes, and this is mediated by high glucose and NADPH oxidase. ..