RRC ID 46638
Author Lo TW, Bennett DC, Goodman SJ, Stern MJ.
Title Caenorhabditis elegans fibroblast growth factor receptor signaling can occur independently of the multi-substrate adaptor FRS2.
Journal Genetics
Abstract The components of receptor tyrosine kinase signaling complexes help to define the specificity of the effects of their activation. The Caenorhabditis elegans fibroblast growth factor receptor (FGFR), EGL-15, regulates a number of processes, including sex myoblast (SM) migration guidance and fluid homeostasis, both of which require a Grb2/Sos/Ras cassette of signaling components. Here we show that SEM-5/Grb2 can bind directly to EGL-15 to mediate SM chemoattraction. A yeast two-hybrid screen identified SEM-5 as able to interact with the carboxy-terminal domain (CTD) of EGL-15, a domain that is specifically required for SM chemoattraction. This interaction requires the SEM-5 SH2-binding motifs present in the CTD (Y(1009) and Y(1087)), and these sites are required for the CTD role of EGL-15 in SM chemoattraction. SEM-5, but not the SEM-5 binding sites located in the CTD, is required for the fluid homeostasis function of EGL-15, indicating that SEM-5 can link to EGL-15 through an alternative mechanism. The multi-substrate adaptor protein FRS2 serves to link vertebrate FGFRs to Grb2. In C. elegans, an FRS2-like gene, rog-1, functions upstream of a Ras/MAPK pathway for oocyte maturation but is not required for EGL-15 function. Thus, unlike the vertebrate FGFRs, which require the multi-substrate adaptor FRS2 to recruit Grb2, EGL-15 can recruit SEM-5/Grb2 directly.
Volume 185(2)
Pages 537-47
Published 2010-6-1
DOI 10.1534/genetics.109.113373
PII genetics.109.113373
PMID 20308281
PMC PMC2881135
MeSH Adaptor Proteins, Signal Transducing Animals Binding Sites / genetics Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Cell Movement / genetics GRB2 Adaptor Protein / genetics GRB2 Adaptor Protein / metabolism GRB2 Adaptor Protein / pharmacology Genes Membrane Proteins Protein Binding / genetics Proteins / chemistry Proteins / genetics Proteins / metabolism* Receptor Protein-Tyrosine Kinases / genetics Receptor Protein-Tyrosine Kinases / metabolism Receptor Protein-Tyrosine Kinases / pharmacology Receptors, Fibroblast Growth Factor / genetics Receptors, Fibroblast Growth Factor / metabolism* Receptors, Fibroblast Growth Factor / physiology* Signal Transduction / drug effects* Signal Transduction / genetics Signal Transduction / physiology*
IF 3.564
Times Cited 5
C.elegans tm1031