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Gene Review

pkc-1  -  Protein PKC-1

Caenorhabditis elegans

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Disease relevance of pkc-1

  • One of the candidate gene products, FEZ1 (fasciculation and elongation protein zeta-1), a protein kinase C (PKC)zeta-interacting protein homologous to the Caenorhabditis elegans synaptic transport protein UNC-76, was found to be up-regulated >30-fold in the resistant R3-2 line [1].

High impact information on pkc-1

  • The predicted amino acid sequence revealed that the predicted tpa-1 protein sequence is highly similar to protein kinase C molecules from various animals, including man [2].
  • Par6 and atypical protein kinase C are key players in the establishment of cell polarity [3].
  • Molecular and pharmacological studies in vitro suggest that protein kinase C (PKC) family members play important roles in intracellular signal transduction [4].
  • These findings confirm that the unc-13 gene product has binding sites similar to those of protein kinase C and may be a component of an alternative transduction pathway of the diacylglycerol signal to a different effector function in the nervous system [5].
  • The defective phenotypes of PKC-3-depleted embryos are similar to those exhibited by mutants for par-3 and another par gene, par-6 [6].

Biological context of pkc-1

  • DKF-1 phosphorylation and activation are unaffected when PKC activity is eliminated by inhibitors [7].
  • Cells engaged in PKC1B gene transcription were identified in transgenic C. elegans that carry the lacZ gene under the regulation of the PKC1B promoter [8].
  • Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-alpha [9].
  • The presence of a C-terminal src homology 3 (SH3) domain and its phosphorylation by casein kinase 2 (CK2) and protein kinase C (PKC) imply a role in signaling [10].
  • During a large-scale screen of a human fetal brain cDNA library, a novel human gene GNB2L1 encoding a novel RACK (receptor of activated protein kinase C) protein was isolated and sequenced [11].

Anatomical context of pkc-1


Associations of pkc-1 with chemical compounds

  • Ca(2+)-dependent activation of nematode PKC was observed in the presence of phosphatidylserine [13].
  • These results suggest that PKC-dependent signaling pathways may promote nicotine adaptation via regulation of nicotinic receptor synthesis or degradation [14].
  • Structure-activity analysis revealed significant but modest differences between recombinant cysteine-rich regions of Unc-13 and PKC delta [15].
  • Inhibition of insulin-induced glucose uptake by atypical protein kinase C isotype-specific interacting protein in 3T3-L1 adipocytes [16].
  • Calphostin C, a compound described as a selective inhibitor of PKC, was also able to inhibit [3H]PDBu binding to Unc-13, suggesting that this inhibitor is not able to distinguish between different classes of phorbol ester receptors [15].

Regulatory relationships of pkc-1

  • Finally, PKC1A and PKC1B mRNA levels are differentially regulated by phorbol esters in a process that may involve the participation of another PKC isoform that is analogous to mammalian PKC delta [17].

Analytical, diagnostic and therapeutic context of pkc-1

  • C. elegans provides an excellent model system for molecular dissection of the cellular signaling pathways involving PKC [12].
  • Endogenous UNC5H1 and PICK1 coimmunoprecipitate from extracts of cultured hippocampal neurons and P4 cortices, and immunohistochemistry shows that UNC5H1, PICK1, and PKC are all present in growth cones [18].
  • The gene was deduced to code for a protein kinase C (PKC) homologue by molecular cloning [19].
  • Ablation of PKC3 function by microinjection of antisense RNA into oocytes yields disorganized, developmentally arrested embryos [20].
  • Animal models in the study of protein kinase C isozymes [21].


  1. Overexpression of fasciculation and elongation protein zeta-1 (FEZ1) induces a post-entry block to retroviruses in cultured cells. Naghavi, M.H., Hatziioannou, T., Gao, G., Goff, S.P. Genes Dev. (2005) [Pubmed]
  2. Mutations in a protein kinase C homolog confer phorbol ester resistance on Caenorhabditis elegans. Tabuse, Y., Nishiwaki, K., Miwa, J. Science (1989) [Pubmed]
  3. Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Etienne-Manneville, S., Hall, A. Curr. Opin. Cell Biol. (2003) [Pubmed]
  4. Diverse regulation of sensory signaling by C. elegans nPKC-epsilon/eta TTX-4. Okochi, Y., Kimura, K.D., Ohta, A., Mori, I. EMBO J. (2005) [Pubmed]
  5. A phorbol ester/diacylglycerol-binding protein encoded by the unc-13 gene of Caenorhabditis elegans. Maruyama, I.N., Brenner, S. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  6. Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans. Tabuse, Y., Izumi, Y., Piano, F., Kemphues, K.J., Miwa, J., Ohno, S. Development (1998) [Pubmed]
  7. Characterization of a novel protein kinase D: Caenorhabditis elegans DKF-1 is activated by translocation-phosphorylation and regulates movement and growth in vivo. Feng, H., Ren, M., Wu, S.L., Hall, D.H., Rubin, C.S. J. Biol. Chem. (2006) [Pubmed]
  8. Structure and expression of a novel, neuronal protein kinase C (PKC1B) from Caenorhabditis elegans. PKC1B is expressed selectively in neurons that receive, transmit, and process environmental signals. Land, M., Islas-Trejo, A., Freedman, J.H., Rubin, C.S. J. Biol. Chem. (1994) [Pubmed]
  9. Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-alpha. Staudinger, J., Lu, J., Olson, E.N. J. Biol. Chem. (1997) [Pubmed]
  10. PACSIN, a brain protein that is upregulated upon differentiation into neuronal cells. Plomann, M., Lange, R., Vopper, G., Cremer, H., Heinlein, U.A., Scheff, S., Baldwin, S.A., Leitges, M., Cramer, M., Paulsson, M., Barthels, D. Eur. J. Biochem. (1998) [Pubmed]
  11. Cloning, expression and genomic structure of a novel human GNB2L1 gene, which encodes a receptor of activated protein kinase C (RACK). Wang, S., Chen, J.Z., Zhang, Z., Gu, S., Ji, C., Tang, R., Ying, K., Xie, Y., Mao, Y. Mol. Biol. Rep. (2003) [Pubmed]
  12. Protein kinase C isotypes in C. elegans. Tabuse, Y. J. Biochem. (2002) [Pubmed]
  13. Purification and characterization of protein kinase C from the nematode Caenorhabditis elegans. Sassa, T., Miwa, J. Biochem. J. (1992) [Pubmed]
  14. Long-term nicotine adaptation in Caenorhabditis elegans involves PKC-dependent changes in nicotinic receptor abundance. Waggoner, L.E., Dickinson, K.A., Poole, D.S., Tabuse, Y., Miwa, J., Schafer, W.R. J. Neurosci. (2000) [Pubmed]
  15. Characterization of the cysteine-rich region of the Caenorhabditis elegans protein Unc-13 as a high affinity phorbol ester receptor. Analysis of ligand-binding interactions, lipid cofactor requirements, and inhibitor sensitivity. Kazanietz, M.G., Lewin, N.E., Bruns, J.D., Blumberg, P.M. J. Biol. Chem. (1995) [Pubmed]
  16. Inhibition of insulin-induced glucose uptake by atypical protein kinase C isotype-specific interacting protein in 3T3-L1 adipocytes. Kotani, K., Ogawa, W., Hashiramoto, M., Onishi, T., Ohno, S., Kasuga, M. J. Biol. Chem. (2000) [Pubmed]
  17. Origin, properties, and regulated expression of multiple mRNAs encoded by the protein kinase C1 gene of Caenorhabditis elegans. Land, M., Islas-Trejo, A., Rubin, C.S. J. Biol. Chem. (1994) [Pubmed]
  18. Surface expression of the netrin receptor UNC5H1 is regulated through a protein kinase C-interacting protein/protein kinase-dependent mechanism. Williams, M.E., Wu, S.C., McKenna, W.L., Hinck, L. J. Neurosci. (2003) [Pubmed]
  19. The tpa-1 gene of Caenorhabditis elegans encodes two proteins similar to Ca(2+)-independent protein kinase Cs: evidence by complete genomic and complementary DNA sequences of the tpa-1 gene. Sano, T., Tabuse, Y., Nishiwaki, K., Miwa, J. J. Mol. Biol. (1995) [Pubmed]
  20. Structure, expression, and properties of an atypical protein kinase C (PKC3) from Caenorhabditis elegans. PKC3 is required for the normal progression of embryogenesis and viability of the organism. Wu, S.L., Staudinger, J., Olson, E.N., Rubin, C.S. J. Biol. Chem. (1998) [Pubmed]
  21. Animal models in the study of protein kinase C isozymes. Choi, D.S., Messing, R.O. Methods Mol. Biol. (2003) [Pubmed]
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