title: Identification of a novel anti-integrin monoclonal antibody that recognises a ligand-induced binding site epitope on the beta 1 subunit.
abstract: Integrins are the major family of receptors involved in the adhesive interactions of cells with extracellular matrix macromolecules. Although it is known that integrins can exist in active or inactive states, the molecular mechanisms by which integrin activity is modulated are poorly understood. A novel anti-integrin monoclonal antibody, 12G10, that enhances alpha 5 beta 1-fibronectin interactions has been identified. 12G10 binds to the beta 1 subunit and appears to recognise a region of the subunit that contains the epitopes of several previously described activating or inhibitory monoclonal antibodies. However, unlike other activating anti-beta 1 antibodies, the binding of 12G10 to alpha 5 beta 1 is increased in the presence of ligands (fibronectin fragment or RGD peptide). This is the first report for the beta 1 integrin family of an antibody that recognises a ligand-induced binding site, and further emphasises the functional importance of a specific region of the beta 1 subunit in regulating integrin-ligand interactions.
authors.affiliation: School of Biological Sciences, University of Manchester, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Mould
authors.forename: A N
authors.initials: AN
authors.lastname: Garratt
authors.forename: J A
authors.initials: JA
authors.lastname: Askari
authors.forename: S K
authors.initials: SK
authors.lastname: Akiyama
authors.forename: M J
authors.initials: MJ
authors.lastname: Humphries
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001665:Binding Sites; D000939:Epitopes / Q000276:immunology*; D005353:Fibronectins / Q000494:pharmacology; D005354:Fibrosarcoma; D006801:Humans; D016023:Integrins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017469:Receptors, Fibronectin / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D005353:Fibronectins; D016023:Integrins; D009842:Oligopeptides; D010446:Peptide Fragments; D017469:Receptors, Fibronectin; C047981:arginyl-glycyl-aspartic acid