let-60 ras INVOLVEMENT IN
egl-15-MEDIATED PROCESSES Michael J. Stern and Estella Chen, Yale University, BCMM 335, P.O. Box 9812, New Haven, CI' 0653~0812, USA. Many signaling events mediated by receptor tyrosine kinases (RTKs) appear to be transduced via the small GTP-binding protein
p21raS. 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 SHVSH3- 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 egI-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-lSa,et) phenotype); and an activity that is required for the expression of the Clear phenotype of clr-l mutants. This last activity is manifested by mutations in
egl-15 that can act as suppressors of clr-l mutants (termed the Soc phenotype). Two indications suggest a possible role of LET-60 Ras in processes mediated by the
egl-15-encoded FGFR First, studies in a vanety of systems have implicated the involvement of Ras in mediating signaling through the FGFR. Second, although there appear~ to be no overlap in EGL15 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 mediated signaling pathways. One way we have tested whether LET 60 Ras acts in EGL-15- mediated processes is to see if a dominant allele of
let-60, nlO46gf, could suppress the phenotypes of
sem-5 and
egl-15 mutants. Scott Clark showed previously that
let-60(
nl046gf) 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(nlO46gf) does not suppress the Soc or SM migration defective phenotypes of sem- 5 mutants that are common to the EGL-15-mediated pathways. For
egl-15 mutants,
let-60(nl O46gf) 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 alldes 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.