Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, People's Republic of China.
IUBMB Life. 2011 Nov;63(11):1037-44. doi: 10.1002/iub.562.
Calcineurin is the only Ca(2+) /calmodulin-dependent serine/threonine protein phosphatase. The roles of the cytosolic calcineurin have been well researched; however, the roles of the serum calcineurin remain unknown. Here, we report that the recombinant human calcineurin B subunit (CnB) can bind to rabbit platelets and show an antiplatelet aggregation activity. Furthermore, CnB exerts an anticoagulant effect by prolonging the activated partial thromboplastin time and thrombin time and reducing the plasma fibrinogen concentration in a dose-dependent manner. We further reveal that the functional domain associated with the anticoagulant activity of CnB is located in the C-terminus. Hemolysis test and intravenous stimulation study show that the recombinant CnB does not cause obvious hemolysis and is safe for intravenous injection. These results reveal a new function of calcineurin B subunit. They also give an explanation for the roles of calcineurin B subunit in serum and point to a possible implication in antithrombotic therapy.
钙调神经磷酸酶是唯一的 Ca(2+) /钙调蛋白依赖性丝氨酸/苏氨酸蛋白磷酸酶。胞质钙调神经磷酸酶的作用已得到充分研究；然而，血清钙调神经磷酸酶的作用仍不清楚。在这里，我们报告重组人钙调神经磷酸酶 B 亚基 (CnB) 可以与兔血小板结合，并显示抗血小板聚集活性。此外，CnB 通过延长激活部分凝血活酶时间和凝血酶时间以及降低纤维蛋白原浓度来发挥抗凝作用，呈剂量依赖性。我们进一步揭示与 CnB 抗凝活性相关的功能域位于 C 末端。溶血试验和静脉刺激研究表明，重组 CnB 不会引起明显的溶血，并且可以安全地静脉注射。这些结果揭示了钙调神经磷酸酶 B 亚基的一个新功能。它们也解释了钙调神经磷酸酶 B 亚基在血清中的作用，并可能暗示其在抗血栓治疗中的作用。
