title: Differential activation of LFA-1 and Mac-1 ligand binding domains.
abstract: Nine integrin alpha subunits contain an 'inserted' or I-domain, known to involve in ligand binding. Mutation of an invariant isoleucine residue in the I-domains of alphaL and alphaM has previously been reported to activate LFA-1 and Mac-1, respectively. In this article, we report notable differences in the regulation of adhesion of these two integrins. We find that mutation of the isoleucine residue in the proposed "socket for isoleucine" in full-length alphaL does not lead to an active LFA-1, although mutation of the equivalent residue in alphaM does convey constitutive activity to Mac-1. In addition, we observe the isolated I-domain of alphaL to be constitutively active. This challenges reports that state the alphaL I-domain exists in an inactive, closed conformation, and requires the presence of activating agents for ligand binding. These results shed further light on the many questions surrounding regulation of integrin activation.
authors.affiliation: The MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Susannah E
authors.initials: SE
authors.lastname: Walters
authors.forename: Ren-Hong
authors.initials: RH
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Cheng
authors.forename: Suet-Mien
authors.initials: SM
authors.lastname: Tan
authors.forename: S K Alex
authors.initials: SK
authors.lastname: Law
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D018845:CD11 Antigens / Q000378:metabolism*; D040881:CD11a Antigen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D039481:CD11b Antigen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D020014:K562 Cells; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry* / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment
chemical_list: D018845:CD11 Antigens; D040881:CD11a Antigen; D039481:CD11b Antigen; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1