title: Affinity modulation of integrin alpha 5 beta 1: regulation of the functional response by soluble fibronectin.
abstract: We report that a beta 1 integrin (alpha 5 beta 1) can exist in different affinity states for its soluble ligand, fibronectin. The alpha 5 beta 1 expressed by the erythroleukemic cell line K562 binds soluble fibronectin with low affinity (Kd > 1 microM), but is induced to bind it with 20-fold higher affinity (Kd-54 nM) in the presence of the anti-beta 1 mAb 8A2. This activation seems to be due to direct antibody-induced change in the receptor that does not require intracellular signaling, and is a plausible basis for the 8A2-induced enhancement of beta 1-dependent adhesion to fibronectin and other immobilized ligands (Kovach, N. L., T. M. Carlos, E. Yee, and J. M. Harlan. 1992. J. Cell Biol. 116: 499-509). Fab fragments of 8A2 bind with higher affinity to alpha 5 beta 1 receptor that is occupied by the GRG-DSP peptide ligand suggesting that the antibody functions by stabilizing a high affinity (occupied) conformer of the receptor. A functional consequence of the affinity modulation is that soluble fibronectin (at physiological concentrations) occupies the high affinity receptors, and so becomes an effective inhibitor of adhesion to immobilized fibronectin. In contrast, the majority of low affinity receptors remain unoccupied and are still to mediate cellular adhesion.
authors.affiliation: Scripps Research Institute, La Jolla, California 92037.
authors.forename: R J
authors.initials: RJ
authors.lastname: Faull
authors.forename: N L
authors.initials: NL
authors.lastname: Kovach
authors.forename: J M
authors.initials: JM
authors.lastname: Harlan
authors.forename: M H
authors.initials: MH
authors.lastname: Ginsberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D002478:Cells, Cultured; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011487:Protein Conformation; D051381:Rats; D017469:Receptors, Fibronectin / Q000378:metabolism*; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D005353:Fibronectins; D017469:Receptors, Fibronectin