Platelet integrin ?IIb?3: signal transduction, regulation, and its therapeutic targeting.

ABSTRACT: Integrins are a family of transmembrane glycoprotein signaling receptors that can transmit bioinformation bidirectionally across the plasma membrane. Integrin ?IIb?3 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 ?IIb?3 also participates in cancer progression, such as tumor cell proliferation and metastasis. In resting platelets, integrin ?IIb?3 adopts an inactive conformation. Upon agonist stimulation, the transduction of inside-out signals leads integrin ?IIb?3 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 ?IIb?3 requires the involvement of numerous interacting proteins, which associate with the cytoplasmic tails of ?IIb?3 in particular. Integrin ?IIb?3 and its signaling pathways are considered promising targets for antithrombotic therapy. This review describes the bidirectional signal transduction of integrin ?IIb?3 in platelets, as well as the proteins responsible for its regulation and therapeutic agents that target integrin ?IIb?3 and its signaling pathways.

SUBMITTER: Huang J 

PROVIDER: S-EPMC6407232 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature