β3 Integrin-Mediated Fibrin Clot Retraction by Nucleated Cells: Differing Behavior of αIIbβ3 and αvβ3

Fibrin clot retraction may be important in resolution of thrombi and, in platelets, is mediated by integrin α IIb β3 (GPIIb-IIIa). Nucleated cells that lack α IIb β3 can retract fibrin clots, and we now report that integrin α v β 3 can support this process. In addition, we compared the capacities of recombinant β 3 integrins to mediate clot retraction in Chinese hamster ovary and M21 melanoma cells. We found that α v β 3 , but not a IIb β 3 , could spontaneously support retraction. Transferring the cytoplasmic domain of α v to α IIb enabled the resulting chimeric α IIb β 3 to support clot retraction. The capacity of the α v cytoplasmic domain to support clot retraction was not caused by activation of the ligand binding function of α IIb β 3 or by enhancement of α IIb β 3 's capacity to stimulate the formation of focal adhesions or the tyrosine phosphorylation of pp125 FAK . These experiments define requirements for α IIb β 3 -mediatind clot retraction, establish the capacity of α v β 3 to mediate this process, and suggest differing functional roles of the α v and α IIb cytoplasmic domains.