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Gene Review

Prkcd  -  protein kinase C, delta

Mus musculus

Synonyms: AI385711, D14Ertd420e, PKC[d], PKCdelta, Pkcd, ...
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Disease relevance of Prkcd


High impact information on Prkcd


Chemical compound and disease context of Prkcd


Biological context of Prkcd

  • Transient-transfection assays with NIH 3T3 cells, using an SRE-driven luciferase reporter plasmid, indicated that PKC-alpha and PKC-epsilon, but not PKC-delta or PKC-zeta, mediate SRE activation [12].
  • The results indicate that UVR-mediated signal transduction pathway to the induction of SCC does not seem to be sensitive to PKCdelta overexpression [13].
  • UVB-induced activation of extracellular signal-regulated protein kinases (Erks) and c-Jun NH2-terminal kinases (JNKs) was strongly inhibited by DNM PKCepsilon and PKCdelta, whereas the DNM of PKCalpha was less effective on the UVB-induced phosphorylation of Erks and JNKs [14].
  • These data demonstrate that PKCdelta and PKCepsilon, but not PKCalpha, mediate UVB-induced signal transduction and apoptosis in JB6 cells through activation of Erks and JNKs [14].
  • Furthermore, rottlerin, an inhibitor of protein kinase Cdelta (PKCdelta) and calmodulin kinase III, abrogated the up-regulation at both protein and mRNA levels [15].

Anatomical context of Prkcd

  • IGF-1 also selectively induced translocation of PKCdelta and PKCepsilon from soluble to particulate fractions in mouse keratinocytes [16].
  • This study showed that UVB markedly induced translocation of membrane-associated PKCepsilon and PKCdelta, but not PKCalpha, from cytosol to membrane [14].
  • Our results suggest that PKCdelta activation is responsible for a major part of EGF-induced fibroblast contractile force generation [17].
  • Similarly, c-Jun amino-terminal kinase activation is suppressed in vivo in gamma-irradiated parotid glands from PKCdelta(-/-) mice [18].
  • In this article we show that PKCzeta but not PKCalpha and PKCdelta can co-immunoprecipitate PKB from CHO cell lysates [19].

Associations of Prkcd with chemical compounds

  • Protein kinase C delta (PKCdelta), a Ca(2+)-independent, phospholipid-dependent serine/threonine kinase, is among the novel PKCs (delta, epsilon, and eta) expressed in mouse epidermis [13].
  • We suggest that the effects of TNF-alpha on IR tyrosine phosphorylation are mediated via alteration of insulin-induced activation and association of PKCdelta and -alpha with upstream signaling molecules [20].
  • Among the PKC inhibitors used only rottlerin, a selective inhibitor of PKCdelta, markedly inhibited the UVB-induced activation of Erks and JNKs, but not p38 kinases [14].
  • PKCdelta was activated by arsenate treatment by in vitro kinase assays [15].
  • In contrast, activation of the c-Jun amino-terminal kinase is reduced in primary parotid cells from PKCdelta(-/-) cells and in parotid C5 cells, which express a dominant inhibitory mutant of PKCdelta [18].
  • The inhibitor of PKCdelta kinase activity rottlerin blocks the translocation of the PKCdelta-Abl complex from the ER to the mitochondria and confers protection against apoptosis [21].

Physical interactions of Prkcd

  • Immunoprecipitation revealed that p53 co-immunoprecipitated with PKC-delta and was phosphorylated at the 15th serine residue in SNP-treated cells [22].
  • HSP25 binds to kinase-active PKCdelta to inhibit its kinase activity and translocation to the membrane, which results in reduced cell death [23].
  • In addition, a fraction of PKC-delta and -eta appears membrane-bound and concentrated in the Golgi apparatus [24].
  • West-Western screening of a cDNA expression library using 32P-labeled, autophosphorylated protein kinase Cdelta (PKCdelta) as a probe, led us to identify cDNA clones encoding a PKCdelta-binding protein that contains a leucine zipper-like motif in its N-terminal region and two PEST sequences in its C-terminal region [25].

Enzymatic interactions of Prkcd

  • PKCdelta (deltaI) is proteolytically cleaved at its hinge region (V3) by caspase 3 and the catalytic fragment is sufficient to induce apoptosis in various cell types [26].
  • The structural requirements of PKC were then examined using a calpain-cleaved active fragment of nPKC delta [27].
  • The PKCdelta that was tyrosine-phosphorylated in response to TGFalpha had reduced activity compared with the nontyrosine-phosphorylated PKCdelta [28].
  • An in vitro kinase assay revealed that p53 was directly phosphorylated by SNP-activated PKC-delta [22].

Regulatory relationships of Prkcd


Other interactions of Prkcd

  • Here we investigate the role of protein kinase Cdelta (PKCdelta) in responses mediated by wild-type murine Kit and the D814Y mutant in a murine mast cell-like line [29].
  • Our results identify PKCdelta and MEK-1 as essential, positive regulators of GLI-mediated HH signaling [33].
  • The inhibition of PKCdelta by rottlerin did not affect the activation of p38 MAPK by arsenate [15].
  • These studies indicate an essential role for PKCdelta downstream of the p53 response and upstream of the c-Jun amino-terminal kinase activation in DNA damage-induced apoptosis in vivo and in vitro [18].
  • Our results suggested that activation of PKCdelta and PKCepsilon provide a negative regulation for Akt phosphorylation and kinase activity in mouse keratinocytes and serve as modulators of cell survival pathways in response to external stimuli [16].

Analytical, diagnostic and therapeutic context of Prkcd

  • Western blot analysis of the amounts of protein kinase C alpha (PKC alpha) and PKC delta in the soluble fraction and the Triton X-100-soluble particulate fraction revealed that translocation of both isozymes from the soluble to the particulate fraction was reversible when the phorbol esters were washed off [34].
  • To determine the domain of PKC-delta that is responsible for this isotype-specific function, cDNAs that encode reciprocal chimeras of PKC-delta and -epsilon (PKC-delta epsilon and PKC-epsilon delta) were constructed by exchanging regulatory and kinase domains using polymerase chain reaction technology [35].
  • Microarray analysis indicated significant changes in expression levels between B6 and 129 mice in the identified chromosomal area of Wnt5a and protein kinase Cdelta (PKCdelta) [36].
  • PKC-delta levels are significantly higher in Tam-resistant tumors compared to Tam-sensitive tumors in xenograft model (P<0.05) [37].
  • Confocal microscopy analysis of LTXBO oocytes during this transition showed PKC-delta associated with the meiotic spindle and then with the chromosomes at MII [38].


  1. Protein kinase Cdelta-mediated proteasomal degradation of MAP kinase phosphatase-1 contributes to glutamate-induced neuronal cell death. Choi, B.H., Hur, E.M., Lee, J.H., Jun, D.J., Kim, K.T. J. Cell. Sci. (2006) [Pubmed]
  2. Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cdelta. Miyamoto, A., Nakayama, K., Imaki, H., Hirose, S., Jiang, Y., Abe, M., Tsukiyama, T., Nagahama, H., Ohno, S., Hatakeyama, S., Nakayama, K.I. Nature (2002) [Pubmed]
  3. Neutrophil protein kinase Cdelta as a mediator of stroke-reperfusion injury. Chou, W.H., Choi, D.S., Zhang, H., Mu, D., McMahon, T., Kharazia, V.N., Lowell, C.A., Ferriero, D.M., Messing, R.O. J. Clin. Invest. (2004) [Pubmed]
  4. Protein kinase C-delta mRNA is down-regulated transcriptionally and post-transcriptionally by 12-O-tetradecanoylphorbol-13-acetate. Shih, N.Y., Floyd-Smith, G. J. Biol. Chem. (1996) [Pubmed]
  5. Distinct roles of c-Abl and Atm in oxidative stress response are mediated by protein kinase C delta. Li, B., Wang, X., Rasheed, N., Hu, Y., Boast, S., Ishii, T., Nakayama, K., Nakayama, K.I., Goff, S.P. Genes Dev. (2004) [Pubmed]
  6. NF-kappaB is required for UV-induced JNK activation via induction of PKCdelta. Liu, J., Yang, D., Minemoto, Y., Leitges, M., Rosner, M.R., Lin, A. Mol. Cell (2006) [Pubmed]
  7. Doxorubicin requires the sequential activation of caspase-2, protein kinase Cdelta, and c-Jun NH2-terminal kinase to induce apoptosis. Panaretakis, T., Laane, E., Pokrovskaja, K., Björklund, A.C., Moustakas, A., Zhivotovsky, B., Heyman, M., Shoshan, M.C., Grandér, D. Mol. Biol. Cell (2005) [Pubmed]
  8. The role of protein kinase C in the regulation of serotonin-2A receptor expression. Anji, A., Sullivan Hanley, N.R., Kumari, M., Hensler, J.G. J. Neurochem. (2001) [Pubmed]
  9. Activation of protein kinase C-delta attenuates kainate-induced cell death of cortical neurons. Jung, Y.S., Lee, B.K., Park, H.S., Shim, J.K., Kim, S.U., Lee, S.H., Baik, E.J., Moon, C.H. Neuroreport (2005) [Pubmed]
  10. Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC-alpha and translocating PKC-delta. Zhang, X.M., Chen, J., Xia, Y.G., Xu, Q. Cancer Chemother. Pharmacol. (2005) [Pubmed]
  11. Roles of tyrosine phosphorylation and cleavage of protein kinase Cdelta in its protective effect against tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis. Okhrimenko, H., Lu, W., Xiang, C., Ju, D., Blumberg, P.M., Gomel, R., Kazimirsky, G., Brodie, C. J. Biol. Chem. (2005) [Pubmed]
  12. Novel roles of specific isoforms of protein kinase C in activation of the c-fos serum response element. Soh, J.W., Lee, E.H., Prywes, R., Weinstein, I.B. Mol. Cell. Biol. (1999) [Pubmed]
  13. Protein kinase C delta overexpressing transgenic mice are resistant to chemically but not to UV radiation-induced development of squamous cell carcinomas: a possible link to specific cytokines and cyclooxygenase-2. Aziz, M.H., Wheeler, D.L., Bhamb, B., Verma, A.K. Cancer Res. (2006) [Pubmed]
  14. Translocation of protein kinase Cepsilon and protein kinase Cdelta to membrane is required for ultraviolet B-induced activation of mitogen-activated protein kinases and apoptosis. Chen, N., Ma, W., Huang, C., Dong, Z. J. Biol. Chem. (1999) [Pubmed]
  15. Pathways of induction of peroxiredoxin I expression in osteoblasts: roles of p38 mitogen-activated protein kinase and protein kinase C. Li, B., Ishii, T., Tan, C.P., Soh, J.W., Goff, S.P. J. Biol. Chem. (2002) [Pubmed]
  16. Protein kinase C negatively regulates Akt activity and modifies UVC-induced apoptosis in mouse keratinocytes. Li, L., Sampat, K., Hu, N., Zakari, J., Yuspa, S.H. J. Biol. Chem. (2006) [Pubmed]
  17. Epidermal growth factor induces fibroblast contractility and motility via a protein kinase C delta-dependent pathway. Iwabu, A., Smith, K., Allen, F.D., Lauffenburger, D.A., Wells, A. J. Biol. Chem. (2004) [Pubmed]
  18. Suppression of apoptosis in the protein kinase Cdelta null mouse in vivo. Humphries, M.J., Limesand, K.H., Schneider, J.C., Nakayama, K.I., Anderson, S.M., Reyland, M.E. J. Biol. Chem. (2006) [Pubmed]
  19. Protein kinase Czeta is a negative regulator of protein kinase B activity. Doornbos, R.P., Theelen, M., van der Hoeven, P.C., van Blitterswijk, W.J., Verkleij, A.J., van Bergen en Henegouwen, P.M. J. Biol. Chem. (1999) [Pubmed]
  20. Differential effects of tumor necrosis factor-alpha on protein kinase C isoforms alpha and delta mediate inhibition of insulin receptor signaling. Rosenzweig, T., Braiman, L., Bak, A., Alt, A., Kuroki, T., Sampson, S.R. Diabetes (2002) [Pubmed]
  21. The PKCdelta -Abl complex communicates ER stress to the mitochondria - an essential step in subsequent apoptosis. Qi, X., Mochly-Rosen, D. J. Cell. Sci. (2008) [Pubmed]
  22. Regulation of p53 by activated protein kinase C-delta during nitric oxide-induced dopaminergic cell death. Lee, S.J., Kim, D.C., Choi, B.H., Ha, H., Kim, K.T. J. Biol. Chem. (2006) [Pubmed]
  23. HSP25 inhibits protein kinase C delta-mediated cell death through direct interaction. Lee, Y.J., Lee, D.H., Cho, C.K., Bae, S., Jhon, G.J., Lee, S.J., Soh, J.W., Lee, Y.S. J. Biol. Chem. (2005) [Pubmed]
  24. Immunocytochemical localization of eight protein kinase C isozymes overexpressed in NIH 3T3 fibroblasts. Isoform-specific association with microfilaments, Golgi, endoplasmic reticulum, and nuclear and cell membranes. Goodnight, J.A., Mischak, H., Kolch, W., Mushinski, J.F. J. Biol. Chem. (1995) [Pubmed]
  25. A protein kinase Cdelta-binding protein SRBC whose expression is induced by serum starvation. Izumi, Y., Hirai, S., Tamai, Y., Fujise-Matsuoka, A., Nishimura, Y., Ohno, S. J. Biol. Chem. (1997) [Pubmed]
  26. PKCdelta alternatively spliced isoforms modulate cellular apoptosis in retinoic acid-induced differentiation of human NT2 cells and mouse embryonic stem cells. Patel, N.A., Song, S.S., Cooper, D.R. Gene Expr. (2006) [Pubmed]
  27. Specificity of the high affinity interaction of protein kinase C with a physiological substrate, myristoylated alanine-rich protein kinase C substrate. Fujise, A., Mizuno, K., Ueda, Y., Osada, S., Hirai, S., Takayanagi, A., Shimizu, N., Owada, M.K., Nakajima, H., Ohno, S. J. Biol. Chem. (1994) [Pubmed]
  28. Activation of the epidermal growth factor receptor signal transduction pathway stimulates tyrosine phosphorylation of protein kinase C delta. Denning, M.F., Dlugosz, A.A., Threadgill, D.W., Magnuson, T., Yuspa, S.H. J. Biol. Chem. (1996) [Pubmed]
  29. PKCdelta plays opposite roles in growth mediated by wild-type Kit and an oncogenic Kit mutant. Jelacic, T., Linnekin, D. Blood (2005) [Pubmed]
  30. Role of protein kinase Cdelta in UV-B-induced apoptosis of macrophages in vitro. Sodhi, A., Sethi, G. Cell. Signal. (2005) [Pubmed]
  31. Regulation of B-cell survival by BAFF-dependent PKCdelta-mediated nuclear signalling. Mecklenbräuker, I., Kalled, S.L., Leitges, M., Mackay, F., Tarakhovsky, A. Nature (2004) [Pubmed]
  32. Protein kinase Cdelta overexpression enhances radiation sensitivity via extracellular regulated protein kinase 1/2 activation, abolishing the radiation-induced G(2)-M arrest. Lee, Y.J., Soh, J.W., Dean, N.M., Cho, C.K., Kim, T.H., Lee, S.J., Lee, Y.S. Cell Growth Differ. (2002) [Pubmed]
  33. Protein kinase C-delta and mitogen-activated protein/extracellular signal-regulated kinase-1 control GLI activation in hedgehog signaling. Riobo, N.A., Haines, G.M., Emerson, C.P. Cancer Res. (2006) [Pubmed]
  34. Dissociation of phorbol esters leads to immediate redistribution to the cytosol of protein kinases C alpha and C delta in mouse keratinocytes. Szallasi, Z., Smith, C.B., Blumberg, P.M. J. Biol. Chem. (1994) [Pubmed]
  35. The catalytic domain of protein kinase C-delta in reciprocal delta and epsilon chimeras mediates phorbol ester-induced macrophage differentiation of mouse promyelocytes. Wang, Q.J., Acs, P., Goodnight, J., Giese, T., Blumberg, P.M., Mischak, H., Mushinski, J.F. J. Biol. Chem. (1997) [Pubmed]
  36. Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice. Almind, K., Kahn, C.R. Diabetes (2004) [Pubmed]
  37. Upregulation of PKC-delta contributes to antiestrogen resistance in mammary tumor cells. Nabha, S.M., Glaros, S., Hong, M., Lykkesfeldt, A.E., Schiff, R., Osborne, K., Reddy, K.B. Oncogene (2005) [Pubmed]
  38. Evidence that protein kinase C (PKC) participates in the meiosis I to meiosis II transition in mouse oocytes. Viveiros, M.M., Hirao, Y., Eppig, J.J. Dev. Biol. (2001) [Pubmed]
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