|
|
Blood, 15 October 2008, Vol. 112, No. 8, pp. 3011-3025.
 Previous Article | Table of Contents | Next Article 
ASH 50TH ANNIVERSARY REVIEW
The GPIIb/IIIa (integrin  IIbβ3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend
Barry S. Coller1, and
Sanford J. Shattil2
1 Laboratory of Blood and Vascular Biology, The Rockefeller University, New York, NY; and
2 Department of Medicine, University of California, San Diego, La Jolla
Starting 90 years ago with a clinical description by Glanzmann of a bleeding disorder associated with a defect in platelet function, technologic advances helped investigators identify the defect as a mutation(s) in the integrin family receptor,  IIbβ3, which has the capacity to bind fibrinogen (and other ligands) and support platelet-platelet interactions (aggregation). The receptor's activation state was found to be under exquisite control, with activators, inhibitors, and elaborate inside-out signaling mechanisms controlling its conformation. Structural biology has produced high-resolution images defining the ligand binding site at the atomic level. Research on IIbβ3 has been bidirectional, with basic insights resulting in improved Glanzmann thrombasthenia carrier detection and prenatal diagnosis, assays to identify single nucleotide polymorphisms responsible for alloimmune neonatal thrombocytopenia, and the development of IIbβ3 antagonists, the first rationally designed antiplatelet agents, to prevent and treat thrombotic cardiovascular disease. The future looks equally bright, with the potential for improved drugs and the application of gene therapy and stem cell biology to address the genetic abnormalities. The IIbβ3 saga serves as a paradigm of rigorous science growing out of careful clinical observations of a rare disorder yielding both important new scientific information and improved diagnosis, therapy, and prevention of other disorders.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. Rivera, M. L. Lozano, L. Navarro-Nunez, and V. Vicente
Platelet receptors and signaling in the dynamics of thrombus formation
Haematologica,
May 1, 2009;
94(5):
700 - 711.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
