Mutations in the Caenorhabditis elegans let-23 EGFR-like gene define elements important for cell-type specificity and function
The Caenorhabditis elegans let-23 gene is a genetically characterized member of the epidermal growth factor receptor (EGFR) tyrosine kinase family. Mutations in let-23 can produce five phenotypes in the nematode. Alleles of let-23 include null alleles, reduction-of-function alleles and alleles that disrupt function in some cell types and not others. We have sequenced some of these mutations to identify sequences and regions important for overall let-23 function and for let-23 function in specific cell types. Our data indicate that in vivo, the receptor's C-terminus can be partitioned into at least three domains that each contribute to receptor function in different cell types. In particular, we find distinct domains that mediate hermaphrodite fertility and vulval induction. Our data also demonstrate for the first time that a single, conserved residue in the ligand binding domain is critical for function in vivo and that mutations in the extracellular cysteines characteristic of the EGFR family can lead to a partial or a complete reduction of receptor function.
© 1994 European Molecular Biology Organization. Received on September 1, 1993. We thank Makota Koga for unpublished let-23 genomic sequence. We also thank Pantelis Tsoulfas, Wendy Fantl, André Brändli, Helen Chamberlin, Andy Golden, Becky Kellum, Bin Liu, Michelle Moritz, Naomi Robinson, Tim Steams and Yixian Zheng for critical reading of this manuscript. G.M.L. was supported by a Merck pre-doctoral fellowship. This research was supported by USPHS grant HD23690 to P.W.S. P.W.S. is an investigator of the Howard Hughes Medical Institute.