RasGAP is involved in signal transduction triggered by FGF1 in Xenopus oocytes expressing FGFR1.
The role of RasGAP was investigated in the model system of Xenopus oocytes expressing fibroblast growth factor receptor 1 (FGFR1) stimulated by fibroblast growth factor 1 (FGF1). The injection of the SH2-SH3-SH2 domains of RasGAP suppressed Ras activity, extracellular signal-regulated protein kinase 2 (ERK2) phosphorylation and Mos synthesis. The SH2 domain of Src, and PP2, an inhibitor of Src, also abolished Ras activity, ERK2 phosphorylation and Mos synthesis. In addition, Src activity was blocked by the SH2-SH3-SH2 domains of RasGAP. Immunoprecipitation of a chimera composed of the extracellular domain of the platelet-derived growth factor (PDGF) receptor and the intracellular domain of FGFR1 stimulated by PDGF-BB demonstrates the recruitment of phosphorylated RasGAP. This study shows that the transduction cascade induced by the FGFR1-FGF1 interaction in Xenopus oocytes involves RasGAP as a co-activator of Src to stimulate the Ras/mitogen-activated protein kinase cascade and Mos synthesis. It emphasises a new positive regulatory role for RasGAP in FGFR transduction.
Cailliau
K
K
Université des Sciences et Technologies de Lille, Laboratoire de Biologie du Développement, UE 1033, Bâtiment SN3, 59655 Cedex, Villeneuve D'Ascq, France. katia.maggio@univ-lille1.fr
Browaeys-Poly
E
E
Vilain
J P
JP
D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism*; D010766:Phosphorylation; D010940:Plant Proteins / Q000378:metabolism; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D017231:Proto-Oncogene Proteins c-mos / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D018075:RNA, Complementary / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis*; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D014981:Xenopus; D020703:ras GTPase-Activating Proteins / Q000737:chemistry* / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism; D018909:src Homology Domains
D004268:DNA-Binding Proteins; D010940:Plant Proteins; D018075:RNA, Complementary; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; C083694:phloem protein-2, Physcomitrella patens; D020703:ras GTPase-Activating Proteins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017479:Receptors, Platelet-Derived Growth Factor; D016392:Proto-Oncogene Proteins pp60(c-src); D017231:Proto-Oncogene Proteins c-mos; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins