title: Identification of a molecular recognition role for the activation loop phosphotyrosine of the SRC tyrosine kinase.
abstract: A human cDNA phage display library screen, using a phosphopeptide designed to mimic the activation loop phosphotyrosine of the Src tyrosine kinase, has identified the N-terminal SH2 domain of the p85 regulatory subunit of phosphatidyl inositol-3 kinase (PI3K) as an interacting recognition domain. Activation loop phosphorylation is known to play a conformational role in kinase activation, but is largely not thought to play a role in protein/protein recognition. Affinity chromatography and biochemical evaluation in mouse fibroblast cells has confirmed the dependence of this interaction on both the Src activation loop phosphotyrosine and the N-terminal SH2 domain of PI3K.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Videlock
authors.forename: Victor K
authors.initials: VK
authors.lastname: Chung
authors.forename: Justin M
authors.initials: JM
authors.lastname: Hall
authors.forename: John
authors.initials: J
authors.lastname: Hines
authors.forename: Christina M
authors.initials: CM
authors.lastname: Agapakis
authors.forename: David J
authors.initials: DJ
authors.lastname: Austin
mesh_terms: D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D019000:Phosphotyrosine / Q000031:analogs & derivatives / Q000378:metabolism*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010748:Phosphopeptides; D019000:Phosphotyrosine; D001710:Biotin; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases