The small proteoglycan decorin supports adhesion and activation of human platelets.
Decorin is a small leucine-rich proteoglycan able to interact with several molecules of the subendothelial matrix, such as collagen and fibronectin. In this work, we investigated the ability of purified decorin to support adhesion of human platelets. We found that gel-filtered platelets were actually able to interact with immobilized decorin. Platelet adhesion to decorin was time dependent, required the presence of Mg(2+) ions, and was totally mediated by the protein core of the proteoglycan. Platelet stimulation with either adenosine diphosphate (ADP) or a thrombin receptor-activating peptide significantly increased interaction of these cells with the proteoglycan. Upon adhesion to immobilized decorin a number of platelet proteins were found to become tyrosine-phosphorylated. By immunoprecipitation experiments with specific antibodies, the tyrosine phosphorylation of the tyrosine kinase Syk and the phospholipase Cgamma2 (PLCgamma2) isozyme was demonstrated in decorin-adherent platelets. Interaction of platelets with decorin was selectively prevented by 2 different antibodies against membrane integrin alpha(2)beta(1), but not by a number of antibodies against other membrane receptors. In addition, integrin alpha(2)beta(1), purified from platelet membranes, was able to specifically interact with immobilized decorin. Finally, purified decorin bound to Sepharose beads could precipitate integrin alpha(2)beta(1) from a platelet membrane glycoprotein preparation. Therefore, these results demonstrate that human platelets can bind to immobilized decorin through integrin alpha(2)beta(1), and that this interaction results in the tyrosine phosphorylation of intracellular proteins.
Guidetti
Gianni
G
Department of Biochemistry, University of Pavia, Italy.
Bertoni
Alessandra
A
Viola
Manuela
M
Tira
Enrica
E
Balduini
Cesare
C
Torti
Mauro
M
D058575:Decorin; D004730:Endothelium, Vascular / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology; D010973:Platelet Adhesiveness; D011485:Protein Binding; D011509:Proteoglycans / Q000737:chemistry / Q000502:physiology*; D038981:Receptors, Collagen
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D016023:Integrins; D011509:Proteoglycans; D038981:Receptors, Collagen