INTEGRIN-ASSOCIATED PROTEIN IS A RECEPTOR FOR THE C-TERMINAL DOMAIN OF THROMBOSPONDIN

The C-terminal ''cell-binding domain'' (CBD) of thrombospondin-1 (TS1) is a binding site for many cell types. Cell-binding peptides based on the sequence RFYVVM from the CBD of TS1 affinity label a 52-kDa cell surface glycoprotein, which we show is integrin-associated protein (IA P or CD47). IAP associates with alpha(v) beta(3) and thereby modulates the activity of several integrins. Cells that express IAP bind strong ly to TS1, the CBD, and its active cell-binding peptides while IAP neg ative cells do not. The 52-kDa protein is affinity labeled on IAP-posi tive but not IAP negative cells, and monoclonal antibodies against IAP specifically immunoprecipitate the affinity-labeled 52-kDa protein fr om lysates of IAP-positive cells. Consistent with the association of I AP with alpha(v) beta(3) integrin, the labeled 52-kDa protein is immun oprecipitated by an anti-alpha(v) beta(3) antibody. Endothelial cells exhibit chemotaxis toward TS1 (at concentrations above 10 nM) and RFYV VM peptides. Chemotaxis to both agents is specifically inhibited by a function blocking anti-IAP monoclonal antibody. These data establish I AP (CD47) as a receptor for the CBD of TS1 and suggest a mechanism for the well established effects of the CBD on cell motility.