PMID:16547100

Citation	Hopper, NA (2006) The adaptor protein soc-1/Gab1 modifies growth factor receptor output in Caenorhabditis elegans. Genetics 173:163-75
Abstract	Previous genetic analysis has shown that dos/soc-1/Gab1 functions positively in receptor tyrosine kinase (RTK)-stimulated Ras/Map kinase signaling through the recruitment of csw/ptp-2/Shp2. Using sensitized assays in Caenorhabditis elegans for let-23/Egfr and daf-2/InsR (insulin receptor-like) signaling, it is shown that soc-1/Gab1 inhibits phospholipase C-gamma (PLCgamma) and phosphatidylinositol 3'-kinase (PI3K)-mediated signaling. Furthermore, as well as stimulating Ras/Map kinase signaling, soc-1/Gab1 stimulates a poorly defined signaling pathway that represses class 2 daf-2 phenotypes. In addition, it is shown that SOC-1 binds the C-terminal SH3 domain of SEM-5. This binding is likely to be functional as the sem-5(n2195)G201R mutation, which disrupts SOC-1 binding, behaves in a qualitatively similar manner to a soc-1 null allele in all assays for let-23/Egfr and daf-2/InsR signaling that were examined. Further genetic analysis suggests that ptp-2/Shp2 mediates the negative function of soc-1/Gab1 in PI3K-mediated signaling, as well as the positive function in Ras/Map kinase signaling. Other effectors of soc-1/Gab1 are likely to inhibit PLCgamma-mediated signaling and stimulate the poorly defined signaling pathway that represses class 2 daf-2 phenotypes. Thus, the recruitment of soc-1/Gab1, and its effectors, into the RTK-signaling complex modifies the cellular response by enhancing Ras/Map kinase signaling while inhibiting PI3K and PLCgamma-mediated signaling.
Links	PubMed PMC1461424 Online version:10.1534/genetics.106.055822
Keywords	Aging/genetics; Amino Acid Sequence; Animals; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/metabolism; Female; Fertility; Larva/metabolism; Longevity/genetics; Molecular Sequence Data; Phenotype; Protein Binding; Receptor, Epidermal Growth Factor/metabolism; Receptor, Insulin/metabolism; Receptors, Growth Factor/metabolism; Signal Transduction; Suppression, Genetic; Vulva/metabolism; src Homology Domains
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