Structure, signal transduction, activation, and inhibition of integrin [alpha]IIb[beta]3

Integrins are heterodimeric receptors comprising [alpha] and [beta] subunits. They are expressed on the cell surface and play key roles in cell adhesion, migration, and growth. Several types of integrins are expressed on the platelets, including [alpha]v[beta]3, [alpha]IIb[beta]3, [alpha]2[beta]1, [alpha]5[beta]1, and [alpha]6[beta]1. Among these, physically [alpha]IIb[beta]3 is exclusively expressed on the platelet surface and their precursor cells, megakaryocytes. [alpha]IIb[beta]3 adopts at least three conformations: i) bent-closed, ii) extended-closed, and iii) extended-open. The transition from conformation i) to iii) occurs when [alpha]IIb[beta]3 is activated by stimulants. Conformation iii) possesses a high ligand affinity, which triggers integrin clustering and platelet aggregation. Platelets are indispensable for maintaining vascular system integrity and preventing bleeding. However, excessive platelet activation can result in myocardial infarction (MI) and stroke. Therefore, finding a novel strategy to stop bleeding without accelerating the risk of thrombosis is important. Regulation of [alpha]IIb[beta]3 activation is vital for this strategy. There are a large number of molecules that facilitate or inhibit [alpha]IIb[beta]3 activation. The interference of these molecules can accurately control the balance between hemostasis and thrombosis. This review describes the structure and signal transduction of [alpha]IIb[beta]3, summarizes the molecules that directly or indirectly affect integrin [alpha]IIb[beta]3 activation, and discusses some novel anti[alpha]IIb[beta]3 drugs. This will advance our understanding of the activation of [alpha]IIb[beta]3 and its essential role in platelet function and tumor development. Keywords: Platelet activation, Integrins, [alpha]IIb[beta]3, Hemostasis, Thrombosis