Thrombin receptors: turning them off after turning them on
Brass, L.F.; Ahuja, M.; Belmonte, E.; Blanchard, N.; Pizarro, S.; Tarver, A.; Hoxie, J.A.
Seminars in Hematology 31(3): 251-260
1994
ISSN/ISBN: 0037-1963 PMID: 7973781 Document Number: 426674
Recent studies have helped to define the mechanisms by which thrombin activates platelets and other cells. Those studies show that the human thrombin receptor has a structure similar to other G protein-coupled receptors, but is activated by a novel mechanism in which thrombin cleaves its receptor, creating a new N-terminus that can serve as a tethered ligand. Shortly after activation, thrombin receptors become temporarily resistant to re-activation. Present evidence suggests that this loss of function is due to a combination of receptor desensitization, phosphorylation and internalization, and that recovery may involve dephosphorylation, as well as receptor recycling and the expression of newly-synthesized receptors. Together these processes provide a potent mechanism for limiting the duration of thrombin-initiated events in platelets and other thrombin-responsive vascular cells.