Contact-dependent signaling during the late events of platelet activation.

Signaling events downstream from collagen receptors and G protein-coupled receptors are responsible for the initiation and extension of platelet plug formation. This creates the platelet plug and hopefully results in the cessation of bleeding. It is not. however, all that is required for hemostasis, and growing evidence is emerging that the perpetuation of a stable hemostatic plug requires additional intracellular signaling. At least part of this process is made possible by the persistent close contacts between platelets that can only occur after the onset of aggregation. This review discusses several examples of such signaling mechanisms that help to perpetuate the platelet plug in a contact-dependent manner, including outside-in signaling through integrins, signaling though Eph kinases and ephrins, and the role of CD40L.