Minding the gaps to promote thrombus growth and stability
Lawrence F. Brass, Li Zhu, Timothy J. Stalker
Lawrence F. Brass, Li Zhu, Timothy J. Stalker
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Review Series

Minding the gaps to promote thrombus growth and stability

Abstract

Efforts to understand the role of platelets in hemostasis and thrombosis have largely focused on the earliest events of platelet activation, those that lead to aggregation. Although much remains to be learned about those early events, this Review examines a later series of events: the interactions between platelets that can only occur once aggregation has begun, bringing platelets into close contact with each other, creating a protected environment in the gaps between aggregated platelets, and fostering the continued growth and stability of the hemostatic plug.

Authors

Lawrence F. Brass, Li Zhu, Timothy J. Stalker

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Eph/ephrin interactions between platelets. Agonists such as thrombin, AD...
Eph/ephrin interactions between platelets. Agonists such as thrombin, ADP, and TxA2 are ligands for G protein–coupled receptors, causing a rapid increase in the cytosolic Ca2+ concentration and producing the inside-out signaling events that lead to integrin αIIbβ3 activation (i). The increasingly stable contacts between platelets permit ephrinB1 to bind to EphA4 and EphB1. As discussed in the text, Eph/ephrin interactions support inside-out signaling by activating Rap1b (ii) and also promote outside-in signaling by promoting the tyrosine phosphorylation of the β subunit of αIIbβ3 (iii).