Document Type
Article
Publication Date
3-2000
Abstract
Genetic factors are believed to influence the development of arterial thromboses. Because integrin alpha(IIb)beta(3) plays a crucial role in thrombus formation, we analyzed receptor adhesive properties using Chinese hamster ovary and human kidney embryonal 293 cells overexpressing the Pl(A1) or Pl(A2) polymorphic forms of alpha(IIb)beta(3). Soluble fibrinogen binding was no different between Pl(A1) and Pl(A2) cells, either in a resting state or when alpha(IIb)beta(3) was activated with anti-LIBS6. Pl(A1) and Pl(A2) cells bound equivalently to immobilized fibronectin. In contrast, significantly more Pl(A2) cells bound to immobilized fibrinogen in an alpha(IIb)beta(3)-dependent manner than did Pl(A1) cells. Disruption of the actin cytoskeleton by cytochalasin D abolished the increased binding of Pl(A2) cells. Compared with Pl(A1) cells, Pl(A2) cells exhibited a greater extent of polymerized actin and cell spreading, enhanced tyrosine phosphorylation of pp125(FAK), and greater fibrin clot retraction. These adhesion differences appear to depend on a signaling mechanism sensitive to receptor occupancy. Thus, the Pl(A2) polymorphism altered integrin-mediated functions of adhesion, spreading, actin cytoskeleton rearrangement, and clot retraction.
Recommended Citation
Vijayan, K Vinod; Goldschmidt-Clermont, Pascal J.; Roos, Christine; and Bray, Paul F., "The Pl(A2) polymorphism of integrin beta(3) enhances outside-in signaling and adhesive functions." (2000). Cardeza Foundation for Hematologic Research. Paper 23.
https://jdc.jefferson.edu/cardeza_foundation/23
Comments
This article has been peer reviewed. It is the author’s final published version in Journal of Clinical Investigation, Volume 105, Issue 6, March 2000, Pages 793-802.
The published version is available at DOI: 10.1172/JCI6982. Copyright © American Society for Clinical Investigation