title: Modulation of the affinity of integrin alpha IIb beta 3 (GPIIb-IIIa) by the cytoplasmic domain of alpha IIb.
abstract: Intracellular signaling alters integrin adhesive functions in inflammation, immune responses, hemostasis, thrombosis, and retinal development. By truncating the cytoplasmic domain of alpha IIb, the affinity of integrin alpha IIb beta 3 for ligand was increased. Reconstitution with the cytoplasmic domain from integrin alpha 5 did not reverse the increased affinity. Thus, the cytoplasmic domain of the alpha subunit of GPIIb-IIIa controls ligand binding affinity, which suggests mechanisms for inside-out transmembrane signaling through integrins. These findings imply the existence of hitherto unappreciated hereditary and acquired thrombotic disorders in humans.
authors.affiliation: Committee on Vascular Biology, Scripps Research Institute, La Jolla, CA 92037.
authors.forename: T E
authors.initials: TE
authors.lastname: O'Toole
authors.forename: D
authors.initials: D
authors.lastname: Mandelman
authors.forename: J
authors.initials: J
authors.lastname: Forsyth
authors.forename: S J
authors.initials: SJ
authors.lastname: Shattil
authors.forename: E F
authors.initials: EF
authors.lastname: Plow
authors.forename: M H
authors.initials: MH
authors.lastname: Ginsberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002449:Cell Aggregation; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: D046911:Macromolecular Substances; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen