title: Rewiring kinase specificity with a synthetic adaptor protein.
abstract: Signaling cascades are managed in time and space by interactions between and among proteins. These interactions are often aided by adaptor proteins, which guide enzyme-substrate pairs into proximity. Miniature proteins are a class of small, well-folded protein domains possessing engineered binding properties. Here we made use of two miniature proteins with complementary binding properties to create a synthetic adaptor protein that effectively redirects a ubiquitous signaling event: tyrosine phosphorylation. We report that miniature-protein-based adaptor 3 uses templated catalysis to redirect the Src family kinase Hck to phosphorylate hDM2, a negative regulator of the p53 tumor suppressor and a poor Hck substrate. Phosphorylation occurs with multiple turnover and at a single site targeted by c-Abl kinase in the cell.
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.
authors.forename: Elissa M
authors.initials: EM
authors.lastname: Hobert
authors.forename: Alanna
authors.initials: A
authors.lastname: Schepartz
mesh_terms: D006801:Humans; D008958:Models, Molecular; D010766:Phosphorylation; D051572:Proto-Oncogene Proteins c-hck / Q000737:chemistry / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
chemical_list: D014443:Tyrosine; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck