Reference - Detail
| 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 | 4.015 |
| Times Cited | 5 |
| WOS Category | GENETICS & HEREDITY |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Resource | |
| C.elegans | tm1031 |