Distinct roles of ligand affinity and cytoskeletal anchorage in αIIbβ3 (GP IIb/IIIa)-mediated cell aggregation and adhesion

Abstract

Platelet integrin αIIbβ3 (GP IIb/IIIa) is functionally modulated by changes in ligand affinity or in cytoskeletal anchorage. CHO cells transfected with wild-type/mutated α IIbβ3 allow the dissection of the relative contributions of the two regulatory mechanisms in αIIbβ 3-mediated adhesion and aggregation. Mutations included a truncation of the cytoplasmic domain of the β-subunit, resulting in a loss of cytoskeletal anchorage of aIIbβ3, and a VGFFK-deletion of the α-subunit, resulting in a permanent high affinity state. αIIbβ3-mediated cell aggregation is dependent on the high affinity state but only partially on the cytoskeletal anchorage of αIIbβ3. In contrast, αIIbβ3-mediated cell adhesio..