Signaling Through Platelet Integrin αIIbβ3: Inside-out, Outside-in, and Sideways
- 1 January 1999
- journal article
- research article
- Published by Georg Thieme Verlag KG in Thrombosis and Haemostasis
- Vol. 82 (08), 318-325
- https://doi.org/10.1055/s-0037-1615849
Abstract
Cell adhesion, which plays a major role in the response of tissues to injury, involves a wide variety of cells, adhesion receptors, and ligands. Prominent among the cells responding to injury are platelets, the first line of defense against hemorrhage and an early player in the overall process of wound-healing.1 Prominent among the adhesion receptors is αIIbβ3, a platelet-specific integrin essential for hemostasis by virtue of its role in mediating platelet aggregation and platelet spreading on vascular matrices. Prominent among the ligands for αIIbβ3 are the multivalent adhesive proteins, fibrinogen and von Willebrand factor (vWF), which in soluble form, mediate platelet aggregation and, in solid phase, mediate adhesive spreading.2 In addition to the adhesive functions of αIIbβ3, this integrin serves as a bidirectional conduit for biochemical and mechanical information flow across the platelet plasma membrane.3 For example, intracellular signals modulate the ligand-binding function of αIIbβ3 (inside-out signaling), and signals generated by ligation and clustering of αIIbβ3 regulate the extent of platelet aggregation and spreading (outside-in signaling). The relationships between αIIbβ3 and intracellular signaling pathways have been the subject of intense study in human platelets, model cell systems, and more recently, in genetically-modified mice. Although model cells and mouse platelets have become indispensable tools to dissect mechanisms of αIIbβ3 signaling, conclusions drawn from their use must always be validated in human platelets. Despite this caveat, a broad, but still incomplete, picture of integrin signaling in platelets is beginning to emerge. This update will highlight selected recent developments in this area and discuss potential clinical implications.Keywords
This publication has 51 references indexed in Scilit:
- Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2.JCI Insight, 1998
- Specific Synergy of Multiple Substrate–Receptor Interactions in Platelet Thrombus Formation under FlowCell, 1998
- A dual thrombin receptor system for platelet activationNature, 1998
- Collagen receptor signalling in platelets: extending the role of the ITAMImmunology Today, 1998
- Inhibition of platelet function by recombinant soluble ecto-ADPase/CD39.JCI Insight, 1998
- Defective platelet activation in Gαq-deficient miceNature, 1997
- Signaling through G Proteins in Platelets: to the Integrins and BeyondThrombosis and Haemostasis, 1997
- An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets. Its influence on glycoprotein IIb-IIIa complex function.JCI Insight, 1995
- Tyrosine kinases and phosphoinositide metabolism in thrombin-stimulated human plateletsBiochemical Journal, 1993
- A patient with platelets deficient in glycoprotein VI that lack both collagen-induced aggregation and adhesion.JCI Insight, 1989