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

Platelets are critical for the maintenance of the integrity of the Vascular system and are the first line of defence against haemorrhage. When they en counter a subendothelial matrix exposed by injury to a vessel, platelets ad here, are activated, anti become adhesive fur other platelets so chat they aggregate. alpha IIb/beta 3, a platelet-specific integrin, is largely promi nent amongst the adhesion receptors and is essential for platelet aggregati on. 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 fi brinogen. Stimulation of platelets with various agonists will induce a conf ormational change in alpha IIb/beta 3 (inside-out signalling). which is the n able to bind soluble fibrinogen resulting in the onset of platelet aggreg ation. However, fibrinogen binding to its membrane receptor is nor simply a passive event allowing the formation of intercellular bridges between plat elets. Indeed, a complex signalling pathway triggered by integrin ligation and clustering (outside-in signalling) will regulate the extent of irrevers ible platelet aggregation and clot retraction. Amongst the signalling enzym es activated downstream of alpha IIb/beta 3 engagement, phosphoinositide 3- kinase plays an important role in the control of the irreversible phase of aggregation. BIOCHEM PHARMACOL 60;8:1069-1074, 2000. (C) 2000 Elsevier Scie nce Inc.