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 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.
Payrastre
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Inserm Unite 326, Hopital Purpan, IFR 30, 31059 Toulouse, France. payrastr@purpan.inserm.fr
Missy
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Trumel
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Bodin
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Plantavid
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Chap
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D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001792:Blood Platelets / Q000378:metabolism*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000502:physiology; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D019869:Phosphatidylinositol 3-Kinases