Integrins and signal transduction: illustration with the alpha(IIb)beta(3)integrin in platelets

The platelet specific integrin, alpha (IIb)beta (3), is largely prominent a mongst the adhesion receptors (80000 copies per platelet) and is essential for platelet aggregation. In resting platelets, alpha (IIb)beta (3) is norm ally in a low activation state, unable to interact with soluble fibrinogen. Stimulation of platelets with various agonists will Induce a conformationa l change of alpha (IIb)beta (3) ("inside-out signalling") is then able to b ind soluble fibrinogen resulting in the onset of platelet aggregation. A co mplex signaling pathway triggered by integrin ligation and clustering ("out side-in signalling") will regulate the extent of irreversible platelet aggr egation and clot retraction. Amongst the signalling enzymes activated downs tream of alpha (IIb)beta (3) engagement, a phosphoinositide 3-kinase plays important role in the control of the irreversible phase of aggregation. Its product, PtSIns(3,4)P-2, appears as a central player in a positive feed-ba ck loop. Indeed, a certain level of integrin engagement is required for its production and, in turn, this lipid influences the strengthening and the i rreversibility of aggregation through the stabilisation of the acto-myosin complexes. The metabolic pathways leading to the integrin-dependent accumul ation of PtdIns(3,4)P-2 and the alpha (IIb)beta (3) associated proteins tha t may regulate the irreversibility platelet aggregation are also discussed in this review.