Caenorhabditis elegans Fibroblast Growth Factor Receptor Signaling Can Occur Independently of the Multi-Substrate Adaptor FRS2

    Authors

    T. W. Lo; D. C. Bennett; S. J. Goodman;M. J. Stern

    Comments

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    Abbreviated Journal Title

    Genetics

    Keywords

    SEX MYOBLAST MIGRATION; DOCKING-PROTEIN FRS2-ALPHA; FGF-RECEPTOR; C-ELEGANS; TYROSINE PHOSPHATASE; GENE SEM-5; PATHWAY; ACTIVATION; DROSOPHILA; TRANSDUCTION; Genetics & Heredity

    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. Ayeast 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.

    Journal Title

    Genetics

    Volume

    185

    Issue/Number

    2

    Publication Date

    1-1-2010

    Document Type

    Article

    Language

    English

    First Page

    537

    Last Page

    U229

    WOS Identifier

    WOS:000281905200012

    ISSN

    0016-6731

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