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Gene Review

DYT10  -  dystonia 10

Homo sapiens

Synonyms: EKD1, PKC
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Disease relevance of PKC


Psychiatry related information on PKC


High impact information on PKC


Chemical compound and disease context of PKC


Biological context of PKC


Anatomical context of PKC


Associations of PKC with chemical compounds

  • Accordingly, the PKC activator phorbol myristate acetate up-regulated LAT expression [23].
  • Protein kinase C epsilon (PKC epsilon), a member of a family of serine/threonine protein kinases, is a transforming oncogene that has been reported to be involved in cell invasion and motility [3].
  • Development of mSCC by the 7,12-dimethylbenz(a)anthracene (100 nmol)-TPA (5 nmol) protocol in PKC epsilon transgenic mice was completely prevented by administration of the suicide inhibitor of ODC alpha-difluoromethylornithine (DFMO, 0.5% w/v) in the drinking water during TPA promotion [4].
  • Increasing PKC epsilon staining intensity was associated with high histologic grade (P = 0.0206), positive Her2/neu receptor status (P = 0.0419), and negative estrogen (P = 0.0026) and progesterone receptor status (P = 0.0008) [3].
  • The rapid stimulatory effect of GnRH-A was blocked by the PKC inhibitor bisindolylmaleimide (GF 109203X) or by down-regulation of endogenous PKC [24].

Physical interactions of PKC

  • Mutation of the alanine residue (Ala-120) to glutamate in the pseudo-substrate region of PKC lambda results in a constitutively active kinase that exhibited more than 2-fold greater binding to FRS2 in vitro than its "closed" wild-type counterpart [25].
  • In addition, overexpression of PKC-delta increased binding of cdk inhibitor p27(Kip1) to cdk4 [26].
  • In the present study we demonstrate that calponin binds directly to the regulatory domain of PKC both in overlay assays and, under native conditions, by sedimentation with lipid vesicles [22].

Enzymatic interactions of PKC

  • VASP is a major substrate for cAMP- and cGMP-regulated protein kinases and it has been shown to be directly phosphorylated on Ser157 by PKC (protein kinase C) [27].
  • PMA activates PKC (protein kinase C) enzymes which phosphorylate IkappaBalpha, leading to its degradation, therefore we used GF109203X to inhibit PKC activity [28].

Regulatory relationships of PKC

  • The combination of AR and IGF1 increases p90(rsk) and Bad phosphorylation as well as inhibiting the conformational change of Bax by a PKC-dependent mechanism [29].
  • Thus, Kv1.3 channels are essential for activation of quiescent cells, but signaling through the PKC pathway enhances expression of IKCa1 channels that are required for continued proliferation [20].
  • PKC phosphorylation regulates PITX2 DNA binding and transcriptional activity [30].
  • Interestingly, PKC-delta inhibition also blocks activation of the p38 MAP kinase, the function of which is required for IFNalpha-dependent transcriptional regulation, suggesting a dual mechanism by which this kinase participates in the generation of IFNalpha responses [31].
  • Parathyroid hormone activates PKC-delta and regulates osteoblastic differentiation via a PLC-independent pathway [32].

Other interactions of PKC

  • Video-EEG monitoring of two affected members suggested that PKC is less likely to be a form of reflex epilepsy, despite the existence of a history of infantile convulsions [2].
  • The association between FRS2 and PKC lambda is likely to be direct as shown by yeast two-hybrid analysis [25].
  • The results show that BMP-2 uses a Smad-independent, PKC-dependent pathway to promote apoptosis via a Bax/Bcl-2 and cytochrome c-caspase-9-caspase-3, -6, -7 cascade in human osteoblasts [33].
  • Consistent with a G1 arrest, increased expression of PKC-delta caused rapid and significant downregulation of cyclin D1 and cyclin E proteins (50% decreases, P<0.05), while mRNA levels remained unchanged [26].
  • Moreover, PKC-delta knockdown enhanced cell proliferation ( approximately 1.4-2-fold, P<0.05) and concomitantly increased cyclin D1 and cyclin E expression ( approximately 1.7-fold, P<0.05) [26].

Analytical, diagnostic and therapeutic context of PKC

  • High-density tissue microarray analysis showed that PKC epsilon protein was detected in 73.6% (106 of 144) of primary tumors from invasive ductal breast cancer patients [3].
  • Severe hair loss observed in PKC epsilon transgenic mice on DFMO during skin tumor promotion has not been reported before in the prevention of cancer in other animal models or in human cancer prevention trials [4].
  • KIT and PKC theta (protein activated in interstitial cells of Cajal and GISTs) expression was determined by western immunoblotting of the total cell lysates from three tumour biopsies [34].
  • Immunoprecipitation of PITX2 and a PITX2 PKC mutant protein reveal specific in vivo phosphorylation by PKC in transfected cells [30].
  • Far-Western blotting revealed that 14-3-3 binds PKC-zeta directly at its regulatory domain, where a S186A mutation in a putative 14-3-3-binding domain strongly reduced the binding and the complex formation with 14-3-3beta and Raf-1 [35].


  1. Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1. Tomita, H., Nagamitsu, S., Wakui, K., Fukushima, Y., Yamada, K., Sadamatsu, M., Masui, A., Konishi, T., Matsuishi, T., Aihara, M., Shimizu, K., Hashimoto, K., Mineta, M., Matsushima, M., Tsujita, T., Saito, M., Tanaka, H., Tsuji, S., Takagi, T., Nakamura, Y., Nanko, S., Kato, N., Nakane, Y., Niikawa, N. Am. J. Hum. Genet. (1999) [Pubmed]
  2. Paroxysmal kinesigenic choreoathetosis: from first discovery in 1892 to genetic linkage with benign familial infantile convulsions. Kato, N., Sadamatsu, M., Kikuchi, T., Niikawa, N., Fukuyama, Y. Epilepsy Res. (2006) [Pubmed]
  3. Protein kinase C epsilon is a predictive biomarker of aggressive breast cancer and a validated target for RNA interference anticancer therapy. Pan, Q., Bao, L.W., Kleer, C.G., Sabel, M.S., Griffith, K.A., Teknos, T.N., Merajver, S.D. Cancer Res. (2005) [Pubmed]
  4. Inhibition of the development of metastatic squamous cell carcinoma in protein kinase C epsilon transgenic mice by alpha-difluoromethylornithine accompanied by marked hair follicle degeneration and hair loss. Wheeler, D.L., Ness, K.J., Oberley, T.D., Verma, A.K. Cancer Res. (2003) [Pubmed]
  5. A caspase-resistant mutant of PKC-delta protects keratinocytes from UV-induced apoptosis. D'Costa, A.M., Denning, M.F. Cell Death Differ. (2005) [Pubmed]
  6. Differential regulation of mRNAs encoding protein kinase C isoenzymes in activated human B cells. Brick-Ghannam, C., Ericson, M.L., Schelle, I., Charron, D. Hum. Immunol. (1994) [Pubmed]
  7. Preprogramming motor dysfunction in paroxysmal kinesigenic choreoathetosis. Fattapposta, F., My, F., Valente, D., Quadrini, R., D'Alessio, C., Amabile, G. Funct. Neurol. (2003) [Pubmed]
  8. Paroxysmal kinesigenic choreoathetosis or hysteria? Waller, D.A. The American journal of psychiatry. (1977) [Pubmed]
  9. Diagnosis of childhood seizure disorders. Murphy, J.V., Dehkharghani, F. Epilepsia (1994) [Pubmed]
  10. Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. Le Good, J.A., Ziegler, W.H., Parekh, D.B., Alessi, D.R., Cohen, P., Parker, P.J. Science (1998) [Pubmed]
  11. Modulation of ion channel activity: a key function of the protein kinase C enzyme family. Shearman, M.S., Sekiguchi, K., Nishizuka, Y. Pharmacol. Rev. (1989) [Pubmed]
  12. CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein. Faris, M., Gaskin, F., Parsons, J.T., Fu, S.M. J. Exp. Med. (1994) [Pubmed]
  13. Tissue kallikrein stimulates Ca(2+) reabsorption via PKC-dependent plasma membrane accumulation of TRPV5. Gkika, D., Topala, C.N., Chang, Q., Picard, N., Th??bault, S., Houillier, P., Hoenderop, J.G., Bindels, R.J. EMBO J. (2006) [Pubmed]
  14. Oxygen alters caveolin-1 and nitric oxide synthase-3 functions in ovine fetal and neonatal lung microvascular endothelial cells. John, T.A., Ibe, B.O., Usha Raj, J. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  15. Regression of ventral striatum hypometabolism after calcium/calcitriol therapy in paroxysmal kinesigenic choreoathetosis due to idiopathic primary hypoparathyroidism. Volonté, M.A., Perani, D., Lanzi, R., Poggi, A., Anchisi, D., Balini, A., Comi, G., Fazio, F. J. Neurol. Neurosurg. Psychiatr. (2001) [Pubmed]
  16. Resveratrol regulates cellular PKC alpha and delta to inhibit growth and induce apoptosis in gastric cancer cells. Atten, M.J., Godoy-Romero, E., Attar, B.M., Milson, T., Zopel, M., Holian, O. Investigational new drugs. (2005) [Pubmed]
  17. The signaling mechanism of ROS in tumor progression. Wu, W.S. Cancer Metastasis Rev. (2006) [Pubmed]
  18. Desensitization of chemokine receptor CCR5 in dendritic cells at the early stage of differentiation by activation of formyl peptide receptors. Le, Y., Wetzel, M.A., Shen, W., Gong, W., Rogers, T.J., Henderson, E.E., Wang, J.M. Clin. Immunol. (2001) [Pubmed]
  19. Interferon alpha induces protein kinase C-epsilon (PKC-epsilon) gene expression and a 4.7-kb PKC-epsilon-related transcript. Wang, C., Constantinescu, S.N., MacEwan, D.J., Strulovici, B., Dekker, L.V., Parker, P.J., Pfeffer, L.M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  20. Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences. Ghanshani, S., Wulff, H., Miller, M.J., Rohm, H., Neben, A., Gutman, G.A., Cahalan, M.D., Chandy, K.G. J. Biol. Chem. (2000) [Pubmed]
  21. Thrombin differentiates normal lung fibroblasts to a myofibroblast phenotype via the proteolytically activated receptor-1 and a protein kinase C-dependent pathway. Bogatkevich, G.S., Tourkina, E., Silver, R.M., Ludwicka-Bradley, A. J. Biol. Chem. (2001) [Pubmed]
  22. Regulation of protein kinase C by the cytoskeletal protein calponin. Leinweber, B., Parissenti, A.M., Gallant, C., Gangopadhyay, S.S., Kirwan-Rhude, A., Leavis, P.C., Morgan, K.G. J. Biol. Chem. (2000) [Pubmed]
  23. Potentiation of CD3-induced expression of the linker for activation of T cells (LAT) by the calcineurin inhibitors cyclosporin A and FK506. Peters, D., Tsuchida, M., Manthei, E.R., Alam, T., Cho, C.S., Knechtle, S.J., Hamawy, M.M. Blood (2000) [Pubmed]
  24. Activation of protein kinase C beta gene expression by gonadotropin-releasing hormone in alpha T3-1 cell line. Role of Ca2+ and autoregulation by protein kinase C. Shraga-Levine, Z., Ben-Menahem, D., Naor, Z. J. Biol. Chem. (1994) [Pubmed]
  25. Association of atypical protein kinase C isotypes with the docker protein FRS2 in fibroblast growth factor signaling. Lim, Y.P., Low, B.C., Lim, J., Wong, E.S., Guy, G.R. J. Biol. Chem. (1999) [Pubmed]
  26. Protein kinase C delta inhibits Caco-2 cell proliferation by selective changes in cell cycle and cell death regulators. Cerda, S.R., Mustafi, R., Little, H., Cohen, G., Khare, S., Moore, C., Majumder, P., Bissonnette, M. Oncogene (2006) [Pubmed]
  27. Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated on Ser157 by protein kinase C-dependent and -independent mechanisms in thrombin-stimulated human platelets. Wentworth, J.K., Pula, G., Poole, A.W. Biochem. J. (2006) [Pubmed]
  28. IkappaBalpha (inhibitory kappaBalpha) identified as labile repressor of MnSOD (manganese superoxide dismutase) expression. Kiningham, K.K., Daosukho, C., St Clair, D.K. Biochem. J. (2004) [Pubmed]
  29. Cooperation of amphiregulin and insulin-like growth factor-1 inhibits Bax- and Bad-mediated apoptosis via a protein kinase C-dependent pathway in non-small cell lung cancer cells. Hurbin, A., Coll, J.L., Dubrez-Daloz, L., Mari, B., Auberger, P., Brambilla, C., Favrot, M.C. J. Biol. Chem. (2005) [Pubmed]
  30. Protein kinase C phosphorylation modulates N- and C-terminal regulatory activities of the PITX2 homeodomain protein. Espinoza, H.M., Ganga, M., Vadlamudi, U., Martin, D.M., Brooks, B.P., Semina, E.V., Murray, J.C., Amendt, B.A. Biochemistry (2005) [Pubmed]
  31. Protein kinase C-delta (PKC-delta ) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727. Uddin, S., Sassano, A., Deb, D.K., Verma, A., Majchrzak, B., Rahman, A., Malik, A.B., Fish, E.N., Platanias, L.C. J. Biol. Chem. (2002) [Pubmed]
  32. Parathyroid hormone activates PKC-delta and regulates osteoblastic differentiation via a PLC-independent pathway. Yang, D., Guo, J., Divieti, P., Bringhurst, F.R. Bone (2006) [Pubmed]
  33. Bone morphogenetic protein-2 promotes osteoblast apoptosis through a Smad-independent, protein kinase C-dependent signaling pathway. Haÿ, E., Lemonnier, J., Fromigué, O., Marie, P.J. J. Biol. Chem. (2001) [Pubmed]
  34. Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) immunoreactivity. Debiec-Rychter, M., Wasag, B., Stul, M., De Wever, I., Van Oosterom, A., Hagemeijer, A., Sciot, R. J. Pathol. (2004) [Pubmed]
  35. 14-3-3 isotypes facilitate coupling of protein kinase C-zeta to Raf-1: negative regulation by 14-3-3 phosphorylation. Van Der Hoeven, P.C., Van Der Wal, J.C., Ruurs, P., Van Dijk, M.C., Van Blitterswijk, J. Biochem. J. (2000) [Pubmed]
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