Worm Breeder's Gazette 13(3): 106 (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.
The egl-15 encoded fibroblast growth factor receptor (FGFR) tyrosine kinase mediates multiple biological processes in C. elegans. egl-15 activity is required for viability, proper sex myoblast migration, and the expression of the Clear phenotype of clr-1 mutants. Genetic analysis suggests that clr-1 acts as a negative regulator of some of the activities of egl-15 .In order to understand this interaction at the molecular level, we cloned and sequenced clr-1 and found that it encodes a receptor-linked protein tyrosine phosphatase (PTP). This suggests that CLR-1 regulates signaling through the FGFR either by dephosphorylation of EGL-15 directly, or of another component of the egl-15 signaling pathway. Thus, the Clear phenotype seems to be due to hyperactivity of FGFR signaling, perhaps due to increased tyrosine phosphorylation.
There are a number of models which may explain why clr-1 only appears to affect a subset of egl-15 phenotypes. One possibility is that PTP activity is specific. For example, CLR-1 may only act on specific tyrosine residues in EGL-15 or downstream signaling components involved in specific pathways. Another possibility is that egl-15 has different functions in different tissues and that clr-1 is only expressed in a subset of these tissues. To distinguish between these two possibilities, we plan to use antibody staining to determine the expression patterns of clr-1 and egl-15 .The antibodies should also be useful to study the interaction of these two molecules biochemically.
Suppressors of clr-1 (Soc) have identified three genes that could encode activators or mediators of egl-15 activity. One of these genes, sem-5 ,encodes an SH2 /SH3containing adaptor protein required to transduce signals from a variety of receptor tyrosine kinases. The function of SEM-5 supports the hypothesis that clr-1 suppressors may mediate signaling through the FGFR. Thus, we have begun to clone the other two soc genes with the hope that their analysis will provide additional insights into FGFR mediated signaling pathways.