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Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting
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Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting
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Journal Article
Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting
2019
Overview
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.
Publisher
BioMed Central,Springer Nature B.V,BMC
Subject
/ Animals
/ Blood Platelets - drug effects
/ Blood Platelets - metabolism
/ Cancer
/ Heart
/ Humans
/ Kindlin
/ Ligands
/ Medicine
/ Oncology
/ Platelet Aggregation Inhibitors - pharmacology
/ Platelet Glycoprotein GPIIb-IIIa Complex - agonists
/ Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors
/ Platelet Glycoprotein GPIIb-IIIa Complex - metabolism
/ Proteins
/ Review
/ Talin
