Activation of alpha(V)beta(3) on vascular cells controls recognition of prothrombin

Citation
Tv. Byzova et Ef. Plow, Activation of alpha(V)beta(3) on vascular cells controls recognition of prothrombin, J CELL BIOL, 143(7), 1998, pp. 2081-2092
Citations number
71
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
00219525 → ACNP
Volume
143
Issue
7
Year of publication
1998
Pages
2081 - 2092
Database
ISI
SICI code
0021-9525(199812)143:7<2081:AOAOVC>2.0.ZU;2-G
Abstract
Regulation of vascular homeostasis depends upon collaboration between cells of the vessel wall and blood coagulation system. A direct interaction betw een integrin alpha(v)beta(3) on endothelial cells and smooth muscle cells a nd prothrombin, the pivotal proenzyme of the blood coagulation system, is d emonstrated and activation of the integrin is required for receptor engagem ent. Evidence that prothrombin is a ligand for alpha(v)beta(3) on these cel ls include: (a) prothrombin binds to purified alpha(v)beta(3) via a RGD rec ognition specificity; (b) prothrombin supports alpha(v)beta(3)-mediated adh esion of stimulated endothelial cells and smooth muscle cells; and (c) endo thelial cells, either in suspension and in a monolayer, recognize soluble p rothrombin via alpha(v)beta(3). alpha(v)beta(3)-mediated cell adhesion to p rothrombin, but not to fibrinogen, required activation of the receptor. Thu s, the functionality of the alpha(v)beta(3) receptor is ligand defined, and prothrombin and fibrinogen represent activation-dependent and activation-i ndependent ligands. Activation of alpha(v)beta(3) could be induced not only by model agonists, PMA and Mn2+, but also by a physiologically relevant ag onist, ADP. Inhibition of protein kinase C and calpain prevented activation of alpha(v)beta(3) on vascular cells, suggesting that these molecules are involved in the inside-out signaling events that activate the integrin. The capacity of alpha(v)beta(3) to interact with prothrombin may play a signif icant role in the maintenance of hemostasis; and, at a general level, ligan d selection by alpha(v)beta(3) may be controlled by the activation state of this integrin.