title: Adaptor protein Nck1 interacts with p120 Ras GTPase-activating protein and regulates its activity.
abstract: Adaptor protein Nck1 binds a number of intracellular proteins and influences various signaling pathways. Here we show that Nck1 directly binds and activates the GTPase-activating protein of Ras (RasGAP), which is responsible for the down-regulation of Ras. The first and the third SH3 domains of Nck1 and the NH(2)-terminal proline-rich sequence of RasGAP contribute most to the complex formation causing direct molecular interaction between the two proteins. Cell adhesion to the substrate is obligatory for the Nck1 and RasGAP association, as cell detachment makes RasGAP incapable of associating with Nck1. This leads to the complex dissipation, decrease of RasGAP activity and the increase of H-Ras-GTP level in the detached cells. Our findings reveal unexpected feature of adaptor protein Nck1 as the regulator of RasGAP activity.
authors.affiliation: Proteomics Centre, Vilnius University Institute of Biochemistry, Lithuania. marija.ger@bchi.vu.lt
authors.forename: Marija
authors.initials: M
authors.lastname: Ger
authors.forename: Zigmantas
authors.initials: Z
authors.lastname: Zitkus
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Valius
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D020134:Catalytic Domain; D002448:Cell Adhesion; D004789:Enzyme Activation; D056945:Hep G2 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D041681:NIH 3T3 Cells; D015513:Oncogene Proteins / Q000378:metabolism*; D017354:Point Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011817:Rabbits; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D014162:Transfection; D020729:p120 GTPase Activating Protein / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C078332:Nck protein; D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D020729:p120 GTPase Activating Protein; D020797:Receptor, Platelet-Derived Growth Factor beta