Molecular evidence for the direct involvement of a protein kinase C in developmental and behavioural susceptibility to tumour-promoting phorbol esters in Caenorhabditis elegans.
The nematode Caenorhabditis elegans displays developmental and behavioural sensitivity to tumour-promoting phorbol esters. This sensitivity involves the gene tpa-1, which encodes two protein kinase C isoforms, TPA-1A and TPA-1B. Here we report the molecular nature of the sensitivity in this animal. Characterization of transposon Tc1-induced phorbol ester-resistant mutants has revealed that Tc1 was inserted in a region encoding the kinase domain, resulting in the loss of tpa-1 products. Introduction of a genomic DNA containing the entire wild-type tpa-1 locus into a Tc1-inserted mutant restored the sensitivity to tumour promoters, and tpa-1 products were also produced. These results suggest that the function of wild-type TPA-1 is necessary and sufficient for tumour promoters to cause developmental and behavioural sensitivity in C. elegans.
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens / Q000494:pharmacology*; D004251:DNA Transposable Elements; D017238:Genes, Helminth; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011493:Protein Kinase C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D017421:Sequence Analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014170:Transformation, Genetic
D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D004251:DNA Transposable Elements; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; C095371:TPA-1 protein, C elegans; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate