Genomes and Genes
Gene Symbol: PKC delta
Description: protein kinase C delta
Alias: ALPS3, CVID9, MAY1, PKCD, nPKC-delta, protein kinase C delta type, protein kinase C delta VIII, tyrosine-protein kinase PRKCD
Products: PKC delta
- Uddin S, Sassano A, Deb D, Verma A, Majchrzak B, Rahman A, et al. Protein kinase C-delta (PKC-delta ) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727. J Biol Chem. 2002;277:14408-16 pubmed..Altogether, these findings indicate that PKC-delta functions as a serine kinase for Stat1 and an upstream regulator of the p38 MAP kinase and plays an important role in the induction of Type I IFN-biological responses. ..
- Bey E, Xu B, Bhattacharjee A, Oldfield C, Zhao X, Li Q, et al. Protein kinase C delta is required for p47phox phosphorylation and translocation in activated human monocytes. J Immunol. 2004;173:5730-8 pubmed..Together, these data suggest that PKCdelta plays a pivotal role in stimulating monocyte NADPH oxidase activity through its regulation of the phosphorylation and translocation of p47phox. ..
- Eitel K, Staiger H, Rieger J, Mischak H, Brandhorst H, Brendel M, et al. Protein kinase C delta activation and translocation to the nucleus are required for fatty acid-induced apoptosis of insulin-secreting cells. Diabetes. 2003;52:991-7 pubmed..These data suggest that nuclear translocation and kinase activity of PKC-delta are both necessary for saturated fatty acid-induced apoptosis. ..
- Iturrioz X, Durgan J, Calleja V, Larijani B, Okuda H, Whelan R, et al. The von Hippel-Lindau tumour-suppressor protein interaction with protein kinase Cdelta. Biochem J. 2006;397:109-20 pubmed..Thus, in contrast with aPKC, PKCdelta is not a conventional substrate of the ubiquitin-ligase complex, VCB-Cul-2, and the observed interaction between these two proteins must underlie a distinct signalling output. ..
- Nakagawa M, Oliva J, Kothapalli D, Fournier A, Assoian R, Kazanietz M. Phorbol ester-induced G1 phase arrest selectively mediated by protein kinase Cdelta-dependent induction of p21. J Biol Chem. 2005;280:33926-34 pubmed..Our results identify a novel link between PKCdelta and G1 arrest via p21 up-regulation and highlight the complexities in the downstream effectors of PKC isozymes in the context of cell cycle progression and proliferation. ..
- Crosby D, Poole A. Physical and functional interaction between protein kinase C delta and Fyn tyrosine kinase in human platelets. J Biol Chem. 2003;278:24533-41 pubmed
- Kambhampati S, Li Y, Verma A, Sassano A, Majchrzak B, Deb D, et al. Activation of protein kinase C delta by all-trans-retinoic acid. J Biol Chem. 2003;278:32544-51 pubmed..In this report, we provide evidence that a member of the protein kinase C (PKC) family of proteins, PKC delta, is activated during RA treatment of the NB-4 and HL-60 acute myeloid leukemia cell lines as well as the MCF-7 ..
- Fan J, Guan S, Cheng C, Cho M, Fields J, Chen M, et al. PKCdelta clustering at the leading edge and mediating growth factor-enhanced, but not ecm-initiated, dermal fibroblast migration. J Invest Dermatol. 2006;126:1233-43 pubmed..Instead, inhibition of PKCdelta blocks PDGF-BB-stimulated activation of signal transducer and activator of transcription 3 (Stat3). This study unveiled the specificity of PKCdelta in the control of DF migration. ..
- Liu J, Chen J, Dai Q, Lee R. Phospholipid scramblase 3 is the mitochondrial target of protein kinase C delta-induced apoptosis. Cancer Res. 2003;63:1153-6 pubmed..These results indicate that PLS3 is a downstream effector of PKC-delta in the mitochondria. ..
- Yoshida K, Miki Y, Kufe D. Activation of SAPK/JNK signaling by protein kinase Cdelta in response to DNA damage. J Biol Chem. 2002;277:48372-8 pubmed..These findings indicate that PKCdelta functions in the activation of SAPK through a Lyn --> PKCdelta --> MEKK1 --> MKK7 --> SAPK signaling cascade in response to DNA damage. ..
- Deucher A, Efimova T, Eckert R. Calcium-dependent involucrin expression is inversely regulated by protein kinase C (PKC)alpha and PKCdelta. J Biol Chem. 2002;277:17032-40 pubmed..These findings suggest that PKCalpha and PKCdelta are required for, and modulate, calcium-dependent keratinocyte differentiation in opposing directions. ..
- Zhu L, Brodie C, Balasubramanian S, Eckert R. Multiple PKCdelta tyrosine residues are required for PKCdelta-dependent activation of involucrin expression--a key role of PKCdelta-Y311. J Invest Dermatol. 2008;128:833-45 pubmed..These findings indicate that PKCdelta activity requires Y(311) and a second tyrosine residue; however, any one of the several tyrosine residues can serve in the secondary role. ..
- Koike K, Fujii T, Nakamura A, Yokoyama G, Yamana H, Kuwano M, et al. Activation of protein kinase C delta induces growth arrest in NPA thyroid cancer cells through extracellular signal-regulated kinase mitogen-activated protein kinase. Thyroid. 2006;16:333-41 pubmed..PKCdelta may therefore be an effective molecular target for novel therapy in thyroid cancer. ..
- Murugappan S, Tuluc F, Dorsam R, Shankar H, Kunapuli S. Differential role of protein kinase C delta isoform in agonist-induced dense granule secretion in human platelets. J Biol Chem. 2004;279:2360-7 pubmed..Furthermore, PKCdelta plays a positive role in protease-activated receptor-mediated dense granule secretion, whereas it functions as a negative regulator downstream of glycoprotein VI signaling. ..
- Storz P, Döppler H, Toker A. Protein kinase Cdelta selectively regulates protein kinase D-dependent activation of NF-kappaB in oxidative stress signaling. Mol Cell Biol. 2004;24:2614-26 pubmed..Once active, the signal is relayed to the activation of NF-kappaB in oxidative stress responses. ..
- Zhao K, Li X, Zhao Q, Huang Y, Li D, Peng Z, et al. Protein kinase Cdelta mediates retinoic acid and phorbol myristate acetate-induced phospholipid scramblase 1 gene expression: its role in leukemic cell differentiation. Blood. 2004;104:3731-8 pubmed..Taken together, these results suggest that as a protein induced upon PKCdelta activation, PLSCR1 is required for ATRA- and PMA-triggered leukemic cell differentiation. ..
- Gao F, Wu Y, Zhao M, Liu C, Wang L, Chen G. Protein kinase C-delta mediates down-regulation of heterogeneous nuclear ribonucleoprotein K protein: involvement in apoptosis induction. Exp Cell Res. 2009;315:3250-8 pubmed publisher..To our knowledge, this is the first demonstration that proteolytically activated PKC-delta down-regulates hnRNP K protein in a proteasome-dependent manner, which plays an important role in apoptosis induction. ..
- Villar J, Arenas M, MacCarthy C, Blánquez M, Tirado O, Notario V. PCPH/ENTPD5 expression enhances the invasiveness of human prostate cancer cells by a protein kinase C delta-dependent mechanism. Cancer Res. 2007;67:10859-68 pubmed..PCPH regulated invasiveness and collagen I expression by a mechanism involving protein kinase C delta (PKC delta): (a) PCPH knockdown in LNCaP cells decreased PKC delta levels relative to control cells; (b) PKC delta ..
- Voss O, Kim S, Wewers M, Doseff A. Regulation of monocyte apoptosis by the protein kinase Cdelta-dependent phosphorylation of caspase-3. J Biol Chem. 2005;280:17371-9 pubmed..Our results provided evidence that the PKCdelta-dependent phosphorylation of caspase-3 provided a novel pro-apoptotic mechanism involved in the regulation of monocyte life span. ..
- Efimova T, Broome A, Eckert R. Protein kinase Cdelta regulates keratinocyte death and survival by regulating activity and subcellular localization of a p38delta-extracellular signal-regulated kinase 1/2 complex. Mol Cell Biol. 2004;24:8167-83 pubmed..This regulation appears to be physiological, since H(2)O(2), a known inducer of keratinocyte apoptosis, promotes identical PKCdelta and p38delta-ERK1/2 activity changes, leading to similar morphological changes. ..
- Zhao Y, He D, Stern R, Usatyuk P, Spannhake E, Salgia R, et al. Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC delta and E-cadherin. Cell Signal. 2007;19:2329-38 pubmed..Pretreatment with LPA reversed HGF-induced c-Met internalization. Overexpression of dominant negative (Dn)-PKC delta or pretreatment with Rottlerin or Pertussis toxin (PTx) attenuated LPA-induced c-Met serine phosphorylation and ..
- Bennasser Y, Bahraoui E. HIV-1 Tat protein induces interleukin-10 in human peripheral blood monocytes: involvement of protein kinase C-betaII and -delta. FASEB J. 2002;16:546-54 pubmed..Altogether, these results suggest that the induction of IL-10 by Tat is strictly dependent on the PKC-delta and -betaII isoforms. ..
- Wolf D, Giese S, Witte V, Krautkrämer E, Trapp S, Sass G, et al. Novel (n)PKC kinases phosphorylate Nef for increased HIV transcription, replication and perinuclear targeting. Virology. 2008;370:45-54 pubmed..We conclude that the activation of nPKCs by Nef is required to increase viral replication/infectivity and direct the subcellular localization of Nef. ..
- Yamanouchi D, Kato K, Ryer E, Zhang F, Liu B. Protein kinase C delta mediates arterial injury responses through regulation of vascular smooth muscle cell apoptosis. Cardiovasc Res. 2010;85:434-43 pubmed publisher..This induction appears to be a mechanism of arterial response that negatively influences the degree of intimal hyperplasia by stimulating VSMC apoptosis. ..
- DeVries T, Kalkofen R, Matassa A, Reyland M. Protein kinase Cdelta regulates apoptosis via activation of STAT1. J Biol Chem. 2004;279:45603-12 pubmed..Our data identify STAT1 as a downstream target of PKCdelta and suggest that PKCdelta may regulate apoptosis by activation of STAT1 target genes. ..
- Lee J, Park J, Kim S, Seo J, Lim K, Jeong J, et al. Protein kinase C-delta regulates the stability of hypoxia-inducible factor-1 alpha under hypoxia. Cancer Sci. 2007;98:1476-81 pubmed..These effects were completely reversed by PKC-delta overexpression following the knockdown of PKC-delta. Collectively, these findings demonstrate the role of PKC-delta as a new regulator of hypoxia-induced angiogenesis. ..
- Zhao X, Xu B, Bhattacharjee A, Oldfield C, Wientjes F, Feldman G, et al. Protein kinase Cdelta regulates p67phox phosphorylation in human monocytes. J Leukoc Biol. 2005;77:414-20 pubmed..Taken together, this is the first report to describe the requirement of PKCdelta in regulating the phosphorylation of p67phox and the related NADPH oxidase activity in primary human monocytes. ..
- Ren J, Datta R, Shioya H, Li Y, Oki E, Biedermann V, et al. p73beta is regulated by protein kinase Cdelta catalytic fragment generated in the apoptotic response to DNA damage. J Biol Chem. 2002;277:33758-65 pubmed..These findings demonstrate that cleavage of PKCdelta to PKCdeltaCF induces apoptosis by a mechanism in part dependent on PKCdeltaCF-mediated phosphorylation of the p73beta Ser-289 site. ..
- Liu Y, Belkina N, Graham C, Shaw S. Independence of protein kinase C-delta activity from activation loop phosphorylation: structural basis and altered functions in cells. J Biol Chem. 2006;281:12102-11 pubmed..Thus, activation loop phosphorylation of PKC-delta may regulate its function in cells in a novel way. ..
- 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. ..
- Lee M, Kim T, Kim Y, Lee S, Ko S, Jong H, et al. The signaling network of transforming growth factor beta1, protein kinase Cdelta, and integrin underlies the spreading and invasiveness of gastric carcinoma cells. Mol Cell Biol. 2005;25:6921-36 pubmed
- Lopez Lluch G, Bird M, Canas B, Godovac Zimmerman J, Ridley A, Segal A, et al. Protein kinase C-delta C2-like domain is a binding site for actin and enables actin redistribution in neutrophils. Biochem J. 2001;357:39-47 pubmed..Microinjection of deltaC2 also inhibits F-actin redistribution. Thus PKC-delta binds to F-actin through its C2 domain, and these interactions are important in regulating actin redistribution in neutrophils. ..
- Fang X, Yu S, Tanyi J, Lu Y, Woodgett J, Mills G. Convergence of multiple signaling cascades at glycogen synthase kinase 3: Edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase C-dependent intracellular pathway. Mol Cell Biol. 2002;22:2099-110 pubmed..LPA and potentially other natural ligands primarily utilize a PKC-dependent pathway to modulate GSK-3. ..
- Matsuoka Y, Hughes C, Bennett V. Adducin regulation. Definition of the calmodulin-binding domain and sites of phosphorylation by protein kinases A and C. J Biol Chem. 1996;271:25157-66 pubmed..These findings suggest a complex reciprocal relationship between regulation of adducin function by calmodulin binding and phosphorylation by PKA and PKC. ..
- Burnette B, Yu G, Felsted R. Phosphorylation of HIV-1 gag proteins by protein kinase C. J Biol Chem. 1993;268:8698-703 pubmed..These data are consistent with the identification of a highly conserved consensus PKC phosphorylation site motif in the HIV-1 gag protein at Ser111 and suggests that PKC phosphorylation plays an important role in gag protein function. ..
- Matsuoka Y, Li X, Bennett V. Adducin is an in vivo substrate for protein kinase C: phosphorylation in the MARCKS-related domain inhibits activity in promoting spectrin-actin complexes and occurs in many cells, including dendritic spines of neurons. J Cell Biol. 1998;142:485-97 pubmed
- Konishi H, Yamauchi E, Taniguchi H, Yamamoto T, Matsuzaki H, Takemura Y, et al. Phosphorylation sites of protein kinase C delta in H2O2-treated cells and its activation by tyrosine kinase in vitro. Proc Natl Acad Sci U S A. 2001;98:6587-92 pubmedProtein kinase C delta (PKC delta) is normally activated by diacylglycerol produced from receptor-mediated hydrolysis of inositol phospholipids...
- Izumi Y, Hirata M, Hasuwa H, Iwamoto R, Umata T, Miyado K, et al. A metalloprotease-disintegrin, MDC9/meltrin-gamma/ADAM9 and PKCdelta are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. EMBO J. 1998;17:7260-72 pubmed..These results suggest that MDC9 and PKCdelta are involved in the stimulus-coupled shedding of the proHB-EGF ectodomain. ..
- Ghayur T, Hugunin M, Talanian R, Ratnofsky S, Quinlan C, Emoto Y, et al. Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis. J Exp Med. 1996;184:2399-404 pubmed..However, the relationship of PKC delta cleavage to induction of apoptosis is unknown...
- Schullery D, Ostrowski J, Denisenko O, Stempka L, Shnyreva M, Suzuki H, et al. Regulated interaction of protein kinase Cdelta with the heterogeneous nuclear ribonucleoprotein K protein. J Biol Chem. 1999;274:15101-9 pubmed..The regulated nature of the PKCdelta-K protein interaction may serve to meet cellular needs at sites of active transcription, RNA processing and translation in response to changing extracellular environment. ..
- Le Good J, Ziegler W, Parekh D, Alessi D, Cohen P, Parker P. Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. Science. 1998;281:2042-5 pubmed..The activation loop phosphorylation of PKCdelta in response to serum stimulation of cells was PI 3-kinase-dependent and was enhanced by PDK1 coexpression. ..
- Bharti A, Kraeft S, Gounder M, Pandey P, Jin S, Yuan Z, et al. Inactivation of DNA-dependent protein kinase by protein kinase Cdelta: implications for apoptosis. Mol Cell Biol. 1998;18:6719-28 pubmed..These findings support the hypothesis that functional interactions between PKCdelta and DNA-PK contribute to DNA damage-induced apoptosis. ..
- Gray J, Burns K, Leas T, Perdew G, Vanden Heuvel J. Regulation of peroxisome proliferator-activated receptor alpha by protein kinase C. Biochemistry. 2005;44:10313-21 pubmed..Together, these studies demonstrate a direct role for PKC in the regulation of PPARalpha, and suggest several PKCs can regulate PPARalpha activity through multiple phosphorylation sites. ..
- Berrón Ruiz L. [Immunological alterations in common variable immunodeficiency]. Rev Alerg Mex. 2017;64:87-108 pubmed
- Sun F, Zhou B, Lin X, Duan L. Proteomic analysis identifies nuclear protein effectors in PKC-delta signaling under high glucose-induced apoptosis in human umbilical vein endothelial cells. Mol Med Rep. 2011;4:865-72 pubmed publisher..Our data show that PKC-delta is an important mediator of cell apoptosis and cell cycle arrest in HUVECs under high glucose stress. ..
- Perillan P, Chen M, Potts E, Simard J. Transforming growth factor-beta 1 regulates Kir2.3 inward rectifier K+ channels via phospholipase C and protein kinase C-delta in reactive astrocytes from adult rat brain. J Biol Chem. 2002;277:1974-80 pubmed..Given the commonality of signaling involving PLC-PKC-delta, we speculate that TGF-beta(1)-evoked depolarization may be an early signaling event related to gene transcription in astrocytes. ..
- Lo R, Cheung H, Wong Y. Constitutively active Galpha16 stimulates STAT3 via a c-Src/JAK- and ERK-dependent mechanism. J Biol Chem. 2003;278:52154-65 pubmed..Demonstration of the involvement of different kinases in Galpha16QL-induced STAT3 activation supports the involvement of multiple signaling pathways in the regulation of transcription by G proteins. ..
- Shu X, Wu W, Mosteller R, Broek D. Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases. Mol Cell Biol. 2002;22:7758-68 pubmed..These data highlight a novel mechanism by which SPK mediates signaling from PKC to Ras in a manner independent of Ras-guanine nucleotide exchange factor. ..
- Zhu B, Zhai J, Zhu H, Kyprianou N. Prohibitin regulates TGF-beta induced apoptosis as a downstream effector of Smad-dependent and -independent signaling. Prostate. 2010;70:17-26 pubmed publisher..These findings suggest a dual role for PHB as a downstream determinant of the cellular response to TGF-beta via Smad-dependent pathway (apoptosis) and MAPK intracellular signaling (survival). ..
- Hew H, Liu H, Lu Z, Kimura J, Miki Y, Yoshida K. Identification of Evi-1 as a novel effector of PKC? in the apoptotic response to DNA damage. Biochim Biophys Acta. 2011;1809:285-94 pubmed publisher..Taken together, we have discovered a novel regulation of Evi-1, which transactivates PLZF, by PKC? to induce cell death in response to genotoxic stress. ..
- Liu C, Lee C, Wei Y. Activation of PKCdelta and ERK1/2 in the sensitivity to UV-induced apoptosis of human cells harboring 4977 bp deletion of mitochondrial DNA. Biochim Biophys Acta. 2009;1792:783-90 pubmed publisher..This may explain, at least in part, the degenerative manifestation of brain and muscle in patients with mitochondrial encephalomyopathies such as CPEO syndrome. ..
- Brandt S, Wessler S, Hartig R, Backert S. Helicobacter pylori activates protein kinase C delta to control Raf in MAP kinase signalling: role in AGS epithelial cell scattering and elongation. Cell Motil Cytoskeleton. 2009;66:874-92 pubmed publisher..Finally, we show that PKC-delta specifically targets Raf kinase to stimulate the Erk1/2 kinase pathway, which is also crucial for phenotypical outcome. Thus, PKC-delta is another important mediator of H. pylori-induced pathogenesis. ..
- Dobransky T, Doherty Kirby A, Kim A, Brewer D, Lajoie G, Rylett R. Protein kinase C isoforms differentially phosphorylate human choline acetyltransferase regulating its catalytic activity. J Biol Chem. 2004;279:52059-68 pubmed..Finally, basal ChAT phosphorylation in neurons is mediated predominantly by PKC at Ser-476, with PKC activation increasing phosphorylation at Ser-440 and enhancing ChAT activity. ..
- Zhu S, Yao F, Li W, Wan J, Zhang Y, Tang Z, et al. PKC?-dependent activation of the ubiquitin proteasome system is responsible for high glucose-induced human breast cancer MCF-7 cell proliferation, migration and invasion. Asian Pac J Cancer Prev. 2013;14:5687-92 pubmed..Our results suggest that PKC?-dependent ubiquitin proteasome system activation plays an important role in high glucose- induced breast cancer cell growth and metastasis. ..
- Orosco A, Fromigue O, Hay E, Marie P, Modrowski D. Dual involvement of protein kinase C delta in apoptosis induced by syndecan-2 in osteoblasts. J Cell Biochem. 2006;98:838-50 pubmed..This establishes a functional interaction between SYND2 and PKCdelta in osteoblasts. ..