SYNERGISTIC ROLES FOR RECEPTOR OCCUPANCY AND AGGREGATION IN INTEGRIN TRANSMEMBRANE FUNCTION

Integrin receptors mediate cell adhesion, signal transduction, and cyt oskeletal organization. How a single transmembrane receptor can fulfil l multiple functions was clarified by comparing roles of receptor occu pancy and aggregation. Integrin occupancy by monovalent ligand induced receptor redistribution, but minimal tyrosine phosphorylation signali ng or cytoskeletal protein redistribution. Aggregation of integrins by noninhibitory monoclonal antibodies on beads induced intracellular ac cumulations of pp125(FAK) and tensin, as well as phosphorylation, but no accumulation of other cytoskeletal proteins such as talin. Combinin g antibody-mediated clustering with monovalent ligand occupancy induce d accumulation of seven cytoskeletal proteins, including alpha-actinin , talin, and F-actin, thereby mimicking multivalent interactions with fibronectin or polyvalent peptides. Integrins therefore mediate a comp lex repertoire of functions through the distinct effects of receptor a ggregation, receptor occupancy, or both together.