Peter Karlheinz, Ahrens Ingo, Schwarz Meike, Bode Christoph, Ylänne Jari
Department of Cardiology and Angiology, University of Freiburg, Freiburg, Germany.
Platelets. 2004 Nov;15(7):427-38. doi: 10.1080/09587100410001723179.
Platelet integrin alphaIIbbeta3 (GP IIb/IIla) is functionally modulated by changes in ligand affinity or in cytoskeletal anchorage. CHO cells transfected with wild-type/mutated alphaIIbbeta3 allow the dissection of the relative contributions of the two regulatory mechanisms in alphaIIbbeta3-mediated adhesion and aggregation. Mutations included a truncation of the cytoplasmic domain of the beta-subunit, resulting in a loss of cytoskeletal anchorage of alphaIIbbeta3, and a VGFFK-deletion of the alpha-subunit, resulting in a permanent high affinity state. alphaIIbbeta3-mediated cell aggregation is dependent on the high affinity state but only partially on the cytoskeletal anchorage of alphaIIbbeta3. In contrast, alphaIIbbeta3-mediated cell adhesion is dependent on the cytoskeletal anchorage but only partially on the high affinity state of alphaIIbbeta3. Thus, the functional evaluation of mutated alphaIIbbeta3 implies a differential role of affinity state and cytoskeletal anchorage for alphaIIbbeta3-mediated cell adhesion and aggregation.
血小板整合素αIIbβ3（糖蛋白IIb/IIIa）通过配体亲和力或细胞骨架锚定的变化进行功能调节。用野生型/突变型αIIbβ3转染的CHO细胞有助于剖析这两种调节机制在αIIbβ3介导的黏附和聚集中的相对贡献。突变包括β亚基胞质结构域的截短，导致αIIbβ3细胞骨架锚定丧失，以及α亚基的VGFFK缺失，导致永久的高亲和力状态。αIIbβ3介导的细胞聚集依赖于高亲和力状态，但仅部分依赖于αIIbβ3的细胞骨架锚定。相反，αIIbβ3介导的细胞黏附依赖于细胞骨架锚定，但仅部分依赖于αIIbβ3的高亲和力状态。因此，对突变型αIIbβ3的功能评估意味着亲和力状态和细胞骨架锚定在αIIbβ3介导的细胞黏附和聚集中具有不同作用。
