The integrin alpha IIb/beta 3 in human platelet signal transduction

• Published in: Biochemical pharmacology 2000-10, Vol.60 (8), p.1069-1074
• Main Authors: Payrastre, B, Missy, K, Trumel, C, Bodin, S, Plantavid, M, Chap, H
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - physiology; Blood Platelets - metabolism; Carrier Proteins - physiology; CD47 Antigen; Humans; Phosphatidylinositol 3-Kinases - physiology; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Receptor, PAR-1; Receptors, Thrombin - physiology; Signal Transduction - physiology
• ISSN: 0006-2952
• DOI: 10.1016/S0006-2952(00)00417-2

Platelets are critical for the maintenance of the integrity of the vascular system and are the first line of defence against haemorrhage. When they encounter a subendothelial matrix exposed by injury to a vessel, platelets adhere, are activated, and become adhesive for other platelets so that they aggregate. alpha IIb/beta 3, a platelet-specific integrin, is largely prominent amongst the adhesion receptors and is essential for platelet aggregation. The ligands for alpha IIb/beta 3 are the multivalent adhesive proteins fibrinogen and von Willebrand factor. In resting platelets, alpha IIb/beta 3 is normally in a low activation state, unable to interact with soluble fibrinogen. Stimulation of platelets with various agonists will induce a conformational change in alpha IIb/beta 3 (inside-out signalling), which is then able to bind soluble fibrinogen resulting in the onset of platelet aggregation. However, fibrinogen binding to its membrane receptor is not simply a passive event allowing the formation of intercellular bridges between platelets. Indeed, a complex signalling pathway triggered by integrin ligation and clustering (outside-in signalling) will regulate the extent of irreversible platelet aggregation and clot retraction. Amongst the signalling enzymes activated downstream of alpha IIb/beta 3 engagement, phosphoinositide 3-kinase plays an important role in the control of the irreversible phase of aggregation.