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.