Brass L F, Ahuja M, Belmonte E, Blanchard N, Pizarro S, Tarver A, Hoxie J A
Department of Medicine, University of Pennsylvania, Philadelphia 19104.
Semin Hematol. 1994 Jul;31(3):251-60.
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.
最近的研究有助于明确凝血酶激活血小板及其他细胞的机制。这些研究表明，人凝血酶受体具有与其他G蛋白偶联受体相似的结构，但通过一种新机制被激活，即凝血酶裂解其受体，产生一个可作为拴系配体的新N端。激活后不久，凝血酶受体暂时对再次激活产生抗性。现有证据表明，这种功能丧失是受体脱敏、磷酸化和内化共同作用的结果，而恢复可能涉及去磷酸化，以及受体再循环和新合成受体的表达。这些过程共同提供了一种有效机制，用于限制血小板和其他凝血酶反应性血管细胞中凝血酶引发事件的持续时间。
