The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily

Abstract

The let-23 gene is required for induction of the Caenorhabditis elegans vulva. It is shown that let-23 encodes a putative tyrosine kinase of the epidermal growth factor receptor subfamily. Thus, let-23 might encode the receptor for the inductive signal required for vulval development. Because let-23 acts upstream of let-60 ras in the vulval determination pathway, the identification of the let-23 product provides support for a link in vivo between tyrosine kinase growth factor receptors and ras proteins in a pathway of cell-type determination.

Signal integration during development: Insights from the Drosophila eye

“…However, Notch-mediated signaling may also directly interfere with the activation state of MAPK. In Caenorhabditis elegans, the RTK LET-23 promotes anchor cell fate in the vulva by activating a canonical Ras/MAPK signaling cassette (Aroian et al, 1990;Wang and Sternberg, 2001). This function is opposed by signaling through the Notch homolog LIN-12 (Greenwald, 1998;Wang and Sternberg, 2001).…”

Isolation and characterization of mammalian homologues of Caenorhabditis elegans lin-7: localization at cell-cell junctions

“…The vulval induction in Caenorhabditis elegans (C. elegans) is a well characterized example of the intercellular signaling between non-neuronal cells. The gonadal anchor cell produces an EGF-like protein, which binds to the let-23 receptor tyrosine kinase (RTK) on the P6.p cell and subsequently activates the RTK/Ras signal cascade (Aroian et al, 1990;Beitel et al, 1990;Han and Sternberg, 1990;Hill and Sternberg, 1992). The precise localization of let-23 RTK at the epithelial junctions is essential for this signaling and requires two PDZ domain-containing proteins.…”

D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene, interacts with the Drosophila EGF receptor in vivo, despite lacking C-terminal adaptor binding sites

“…Interestingly, recent observations indicate that the C. elegans c-Cbl homologue, sli-1, acts as a negative regulator of the nematode homologue of the EGF receptor, LET-23 Yoon et al, 1995). LET-23, is required for the induction of vulval cell fates from precursor cells (Aroian et al, 1990) and animals carrying let-23 lossof-function alleles display a vulvaless phenotype. sli-1 was isolated in a genetic screen for suppressors of a partial loss-of-function let-23 allele.…”