Integrins are a family of transmembrane
glycoprotein signaling receptors that can transmit bioinformation bidirectionally across the plasma membrane.
Integrin αIIbβ3 is expressed at a high level in platelets and their progenitors, where it plays a central role in platelet functions, hemostasis, and arterial
thrombosis.
Integrin αIIbβ3 also participates in
cancer progression, such as
tumor cell proliferation and
metastasis. In resting platelets,
integrin αIIbβ3 adopts an inactive conformation. Upon agonist stimulation, the transduction of inside-out signals leads
integrin αIIbβ3 to switch from a low- to high-affinity state for
fibrinogen and other
ligands.
Ligand binding causes
integrin clustering and subsequently promotes outside-in signaling, which initiates and amplifies a range of cellular events to drive essential platelet functions such as spreading, aggregation, clot retraction, and
thrombus consolidation. Regulation of the bidirectional signaling of
integrin αIIbβ3 requires the involvement of numerous interacting
proteins, which associate with the cytoplasmic tails of αIIbβ3 in particular.
Integrin αIIbβ3 and its signaling pathways are considered promising targets for antithrombotic
therapy. This review describes the bidirectional signal transduction of
integrin αIIbβ3 in platelets, as well as the
proteins responsible for its regulation and therapeutic agents that target
integrin αIIbβ3 and its signaling pathways.