A POINT MUTATION IN THE EXTRACELLULAR DOMAIN ACTIVATES LET-23, THE CAENORHABDITIS-ELEGANS EPIDERMAL GROWTH-FACTOR RECEPTOR HOMOLOG

The let-23 gene encodes a Caenorhabditis elegans homolog of the epider mal growth factor receptor (EGFR) necessary for vulval development. We have characterized a mutation of let-23 that activates the receptor a nd downstream signal transduction, leading to excess vulval differenti ation. This mutation alters a conserved cysteine residue in the extrac ellular domain and is the first such point mutation in the EGFR subfam ily of tyrosine kinases. Mutation of a different cysteine in the same subdomain causes a strong loss-of-function phenotype, suggesting that cysteines in this region are important for function and nonequivalent. Vulval precursor cells can generate either of two subsets of vulval c ells (distinct fates) in response to sa62 activity. The fates produced depended on the copy number of the mutation, suggesting that quantita tive differences in receptor activity influence the decision between t hese two fates.