The adaptor protein soc-1/Gab1 modifies growth factor receptor output in Caenorhabditis elegans.
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.
School of Biological Sciences, University of Southampton, Southampton SO16 7PX, United Kingdom. nah2@soton.ac.uk
Neil A
NA
Hopper
D000375:Aging / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005298:Fertility; D007814:Larva / Q000378:metabolism; D008136:Longevity / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D011485:Protein Binding; D011972:Receptor, Insulin / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013489:Suppression, Genetic; D014844:Vulva / Q000378:metabolism; D018909:src Homology Domains
D029742:Caenorhabditis elegans Proteins; D017978:Receptors, Growth Factor; C085751:Sem-5 protein, C elegans; C439708:soc-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D066246:ErbB Receptors; D011972:Receptor, Insulin