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© The Rockefeller University Press, 0021-9525/1998//2081 $5.00
The Journal of Cell Biology, Volume 143, Number 7, , 1998 2081-2092

Regular Articles

Activation of {alpha}Vβ3 on Vascular Cells Controls Recognition of Prothrombin



Tatiana V. Byzova and Edward F. Plow

Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195

Regulation of vascular homeostasis depends upon collaboration between cells of the vessel wall and blood coagulation system. A direct interaction between integrin {alpha}Vβ3 on endothelial cells and smooth muscle cells and prothrombin, the pivotal proenzyme of the blood coagulation system, is demonstrated and activation of the integrin is required for receptor engagement. Evidence that prothrombin is a ligand for {alpha}Vβ3 on these cells include: (a) prothrombin binds to purified {alpha}Vβ3 via a RGD recognition specificity; (b) prothrombin supports {alpha}Vβ3-mediated adhesion of stimulated endothelial cells and smooth muscle cells; and (c) endothelial cells, either in suspension and in a monolayer, recognize soluble prothrombin via {alpha}Vβ3. {alpha}Vβ3-mediated cell adhesion to prothrombin, but not to fibrinogen, required activation of the receptor. Thus, the functionality of the {alpha}Vβ3 receptor is ligand defined, and prothrombin and fibrinogen represent activation- dependent and activation-independent ligands. Activation of {alpha}Vβ3 could be induced not only by model agonists, PMA and Mn2+, but also by a physiologically relevant agonist, ADP. Inhibition of protein kinase C and calpain prevented activation of {alpha}Vβ3 on vascular cells, suggesting that these molecules are involved in the inside-out signaling events that activate the integrin. The capacity of {alpha}Vβ3 to interact with prothrombin may play a significant role in the maintenance of hemostasis; and, at a general level, ligand selection by {alpha}Vβ3 may be controlled by the activation state of this integrin.

Key Words: integrins • endothelial cells • smooth muscle cells • cell adhesion • ligands

Abbreviations used in this paper: HAEC, human aortic endothelial cells; HASMC, human aortic smooth muscle cells; HUVEC, human umbilical vein endothelial cells; PKC, protein kinase C; RGD, Arg-Gly-Asp.


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