Thrombospondin-1 acts via IAP/CD47 to synergize with collagen in alpha2beta1-mediated platelet activation.
Integrin-associated protein (IAP; or CD47) is a receptor for the cell binding domain (CBD) of thrombospondin-1 (TS1). In platelets, IAP associates with and regulates the function of alphaIIbbeta3 integrin (Chung et al, J Biol Chem 272:14740, 1997). We test here the possibility that CD47 may also modulate the function of platelet integrin alpha2beta1, a collagen receptor. The CD47 agonist peptide, 4N1K (KRFYVVMWKK), derived from the CBD, synergizes with soluble collagen in aggregating platelet-rich plasma. 4N1K and intact TS1 also induce the aggregation of washed, unstirred platelets on immobilized collagen with a rapid increase in tyrosine phosphorylation. The effects of TS1 and 4N1K on platelet aggregation are absolutely dependent on IAP, as shown by the use of platelets from IAP-/- mice. Prostaglandin E1 (PGE1) prevents 4N1K-dependent aggregation on immobilized collagen but does not inhibit the 4N1K peptide stimulation of alpha2beta1-dependent platelet spreading. Finally, a detergent-stable, physical association of IAP and alpha2beta1 integrin is detected by coimmunoprecipitation. These results imply a role for IAP and TS1 in the early activation of platelets upon adhesion to collagen.
Chung
J
J
Department of Biochemistry and Molecular Biophysics and Internal Medicine, Washington University School of Medicine, St Louis, MO, USA.
Wang
X Q
XQ
Lindberg
F P
FP
Frazier
W A
WA
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000187:drug effects* / Q000494:pharmacology; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000187:drug effects* / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology*; D003902:Detergents / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D046911:Macromolecular Substances; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D038981:Receptors, Collagen; D019700:Thrombospondin 1 / Q000494:pharmacology*
C120273:4N1K peptide; D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; C497895:Cd47 protein, mouse; D003902:Detergents; D016023:Integrins; D046911:Macromolecular Substances; D009842:Oligopeptides; D010446:Peptide Fragments; D038981:Receptors, Collagen; D019700:Thrombospondin 1; C082835:thrombin receptor peptide (42-47); D003094:Collagen; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline; C058347:glycyl-arginyl-glycyl-glutamyl-seryl-proline; D000527:Alprostadil