Worm Breeder's Gazette 13(3): 105 (June 1, 1994)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Many signaling events mediated by receptor tyrosine kinases (RTKs) appear to be transduced via the small GTP-binding protein p21 (ras).In C. elegans, signaling through LET-23 ,an RTK of the epidermal growth factor receptor subfamily, appears to be mediated by the Ras homolog LET-60 .The SH2 /SH3-containing"adaptor" protein SEM-5 is also involved in this pathway and has been proposed to transduce the signal from LET-23 to LET-60 Ras. Mutations affecting these components have shown that they are involved in a number of processes including vulval induction and an essential process whose disruption results in a rod-like larval lethality.
We have shown that egl-15 encodes an RTK of the fibroblast growth factor receptor (FGFR) subfamily (1993 C. elegans meeting abstracts, p. 104). egl-15 is involved in three known processes: a signaling process that guides the sex myoblast (SM) cell migrations; an essential process whose perturbation results in an early larval arrest (termed the Egl-15 (Let)phenotype); and an activity that is required for the expression of the Clear phenotype of clr-1 mutants. This last activity is manifested by mutations in egl-15 that can act as suppressors of clr-1 mutants (termed the Soc phenotype).
Two indications suggest a possible role of LET-60 Ras in processes mediated by the egl-15 -encodedFGFR. First, studies in a variety of systems have implicated the involvement of Ras in mediating signaling through the FGFR. Second, although there appears to be no overlap in EGL-15 and LET-23 function, the "adaptor" protein SEM-5 appears to mediate signaling by both receptors. LET 60 Ras appears to act downstream of the LET-23 RTK Therefore, we have tested the possible role of LET-60 Ras in EGL-15 -mediatedsignaling pathways.
One way we have tested whether LET-60 Ras acts in EGL-15 -mediatedprocesses is to see if a dominant allele of let-60 , n1046 gf,could suppress the phenotypes of sem-5 and egl-15 mutants. The data from these experiments are shown in the following table.
Scott Clark showed previously that let-60 ( n1046 gf)efficiently suppresses the vulvaless and rod-like larval lethal phenotypes of sem-5 mutants similar to its effects on let-23 mutants. By contrast, let-60 ( n1046 gf)does not suppress the Soc or SM migration defective phenotypes of sem-5 mutants that are common to the EGL-15 -mediatedpathways. For egl-15 mutants, let-60 ( n1046 gf)also fails to suppress the Soc phenotype and can only partially suppress the larval arrest and migration defects.
Secondly, we have conducted a screen for SM migration mutants in a genetic background that has been shown to sensitize the animals to mutations that otherwise have little or no effect on SM migration. While mutations in unc-53 , unc-71 ,and unc-73 were identified in this screen (1993 C. elegans meeting abstracts, p. 168), no mutations in vulval induction genes were isolated. Furthermore, representative hypomorphic alleles of let 60 show no SM migration defect either on their own or in this sensitized background.
The partial suppression of two egl-15 phenotypes suggests that LET-60 may play a minor role in EGL-15 mediated processes. However, these data provide no evidence for a major role for LET-60 in this pathway.