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 (IAP or CD47). IAP associates with alpha v beta 3 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 alpha v beta 3 integrin, the labeled 52-kDa protein is immunoprecipitated by an anti-alpha v beta 3 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.
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
A G
AG
Gao
F P
FP
Lindberg
M B
MB
Finn
S D
SD
Blystone
E J
EJ
Brown
W A
WA
Frazier
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D019699:Thrombospondins; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D016023:Integrins; D008562:Membrane Glycoproteins; D019699:Thrombospondins