title: Engineering NGF receptors to bind Grb2 directly uncovers differences in signaling ability between Grb2- and ShcA-binding sites.
abstract: Grb2 and ShcA are two phosphotyrosine-binding proteins that link receptor protein-tyrosine kinases to activation of the Ras-Erk pathway. While some receptors bind Grb2 directly, others bind ShcA, which provides a binding site for Grb2. In order to compare signal transduction through a Grb2-binding site with signal transduction through a ShcA-binding site, we replaced the ShcA-binding site in the NGF receptor with a Grb2-binding site. Our results show that the Grb2- and ShcA-binding sites have similar abilities to activate the Ras-Erk and PI 3-kinase-Akt pathways. In contrast, they displayed dramatic differences in their ability to activate DNA synthesis.
authors.affiliation: Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Dr., San Diego, CA 92182-1030, United States.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Oku
authors.forename: Talitha
authors.initials: T
authors.lastname: van der Meulen
authors.forename: Jeremy
authors.initials: J
authors.lastname: Copp
authors.forename: Gary
authors.initials: G
authors.lastname: Glenn
authors.forename: Peter
authors.initials: P
authors.lastname: van der Geer
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000096:biosynthesis; D051380:GRB2 Adaptor Protein / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
chemical_list: D051380:GRB2 Adaptor Protein; D020800:Receptor, Nerve Growth Factor; D055765:Shc Signaling Adaptor Proteins; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018631:ras Proteins