MOLECULAR EVIDENCE FAT THE DIRECT INVOLVEMENT OF A PROTEIN-KINASE-C IN DEVELOPMENTAL AND BEHAVIORAL SUSCEPTIBILITY TO TUMOR-PROMOTING PHORBOL ESTERS IN CAENORHABDITIS-ELEGANS

The nematode Caenorhabditis elegans displays developmental and behavio ural 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 sensitiv ity in this animal. Characterization of transposon Tc1-induced phorbol ester-resistant mutants has revealed that Tc1 was inserted in a regio n encoding the kinase domain, resulting in the loss of tpa-1 products. Introduction of a genomic DNA containing the entire wild-type tpa-1 l ocus into a Tc1-inserted mutant restored the sensitivity to tumour pro moters, and tpa-1 products were also produced. These results suggest t hat the function of wild-type TPA-1 is necessary and sufficient for tu mour promoters to cause developmental and behavioural sensitivity in C -elegans.