An integrin receptor on normal and thrombasthenic platelets that binds thrombospondin.
The members of the integrin family of membrane glycoprotein heterodimer complexes function as cell surface receptors for adhesive proteins. We report here on the identification of two integrins on the surface of human platelets that bind to thrombospondin. When platelet membrane proteins are radiolabeled with 125I-lactoperoxidase, solubilized in n-octylglucoside, (Boehringer Mannheim Biochemicals, Indianapolis, IN), and applied to a column of thrombospondin-Sepharose, both complexes are bound to the column and specifically eluted with the peptide GRGDSP. One of these integrins, glycoprotein (GP) IIb-IIIa, appears to bind relatively weakly. The second integrin shares the same beta subunit (beta 3 or GPIIIa), but has a distinct alpha subunit that comigrates with the alpha subunit (alpha v) of the vitronectin receptor (VnR) on endothelial cells and reacts with a monoclonal antibody, LM142, which was raised against an integrin from M21 melanoma cells. The alpha v beta 3 integrin is present on a variety of cell types and appears to act as a receptor for thrombospondin on endothelial and smooth muscle cells. On endothelial and M21 melanoma cells this receptor is also involved in adhesion to fibrinogen, vitronectin, and von Willebrand factor (vWF). The alpha v beta 3 integrin is present at approximately equal levels on normal and thrombasthenic platelets, whereas levels of GPIIb-IIIa are greatly reduced on thrombasthenic platelets. The alpha v beta 3 integrin on thrombasthenic platelets also binds to thrombospondin-Sepharose and can be eluted with the peptide GRGDSP. These data indicate that the alpha v beta 3 integrin on platelets, endothelial cells, and smooth muscle cells functions as an Arg-Gly-Asp (RGD)-dependent receptor for thrombospondin.
Lawler
J
J
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
Hynes
R O
RO
D001791:Blood Platelet Disorders / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D018955:CD36 Antigens; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008970:Molecular Weight; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D016024:Receptors, Cytoadhesin / Q000378:metabolism*; D013915:Thrombasthenia / Q000097:blood*; D019699:Thrombospondins
D018955:CD36 Antigens; D016023:Integrins; D008562:Membrane Glycoproteins; D010980:Platelet Membrane Glycoproteins; D016024:Receptors, Cytoadhesin; D019699:Thrombospondins