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J. Cell Biol.,
Volume 143, Number 7, December 28, 1998 2081-2092
V
3 on Vascular Cells Controls
Recognition of Prothrombin
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 
V
3 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 V3
on these cells include: (a) prothrombin binds to purified
V3 via a RGD recognition specificity; (b) prothrombin supports V3-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 V3. V3-mediated
cell adhesion to prothrombin, but not to fibrinogen,
required activation of the receptor. Thus, the functionality of the V3 receptor is ligand defined, and prothrombin and fibrinogen represent activation-
dependent and activation-independent ligands.
Activation of V3 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 V3 on vascular
cells, suggesting that these molecules are involved in the inside-out signaling events that activate the integrin.
The capacity of V3 to interact with prothrombin may
play a significant role in the maintenance of hemostasis;
and, at a general level, ligand selection by V3 may be
controlled by the activation state of this integrin.
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