Structure, signal transduction, activation, and inhibition of integrin IIb3

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.