Membranes and Bioenergetics
Integrin-associated Protein Is a Receptor for the C-terminal Domain of Thrombospondin (∗)

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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 (IAP or CD47). IAP associates with αvβ3 and thereby modulates the activity of several integrins. Cells that express IAP bind strongly to TS1, the CBD, and its active cell-binding peptides while IAP negative cells do not. The 52-kDa protein is affinity labeled on IAP-positive but not IAP-negative cells, and monoclonal antibodies against IAP specifically immunoprecipitate the affinity-labeled 52-kDa protein from lysates of IAP-positive cells. Consistent with the association of IAP with αvβ3 integrin, the labeled 52-kDa protein is immunoprecipitated by an anti-αvβ3 antibody. Endothelial cells exhibit chemotaxis toward TS1 (at concentrations above 10 nM) and RFYVVM peptides. Chemotaxis to both agents is specifically inhibited by a function blocking anti-IAP monoclonal antibody. These data establish IAP (CD47) as a receptor for the CBD of TS1 and suggest a mechanism for the well established effects of the CBD on cell motility.

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This work was supported by grants from the National Institutes of Health (to E. J. B. and W. A. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Howard Hughes postdoctoral fellow during this work and currently an investigator of the Arthritis Foundation.

Supported by National Institutes of Health Grant F32-AI-08990 and a grant from the Lucille P. Markey Foundation.