Hwang J, Bragado M J, Duan R D, Williams J A
Department of Physiology, University of Michigan, Ann Arbor 48109-0622, USA.
Biochem Biophys Res Commun. 1996 Aug 14;225(2):520-4. doi: 10.1006/bbrc.1996.1205.
Cholecystokinin (CCK) is known to rapidly and transiently increase both [Ca2+]i and autonomous CaM kinase II activity in rat pancreatic acini. Because induction of autonomous activity may involve intramolecular autophosphorylation, the effects of protein phosphatase inhibitors were examined. None of the inhibitors tested (okadaic acid, calyculin A, and cyclosporin A) affected basal activity. Okadaic acid, a potent inhibitor of PP2A and weaker inhibitor of PP1, increased the peak autonomous activity by 30% over the level normally induced by CCK alone, while calyculin A, a potent inhibitor of both PP1 and PP2A, showed an even greater increase of 97%. Both inhibitors also delayed the decline of autonomous activity and calyculin A had a more potent effect than okadaic acid. Cyclosporin A, an inhibitor of PP2B, had no effect. The data indicate that PP1 may be involved in the dephosphorylation of CaMK II and decline of autonomous activity.
已知胆囊收缩素（CCK）可迅速且短暂地增加大鼠胰腺腺泡中的细胞内钙离子浓度（[Ca2+]i）和自主钙调蛋白激酶II（CaM kinase II）的活性。由于自主活性的诱导可能涉及分子内自磷酸化，因此研究了蛋白磷酸酶抑制剂的作用。所测试的抑制剂（冈田酸、花萼海绵诱癌素A和环孢菌素A）均未影响基础活性。冈田酸是蛋白磷酸酶2A（PP2A）的强效抑制剂，对蛋白磷酸酶1（PP1）的抑制作用较弱，与单独使用CCK正常诱导的水平相比，其使自主活性峰值提高了30%，而花萼海绵诱癌素A是PP1和PP2A的强效抑制剂，其使自主活性提高了97%，增幅更大。两种抑制剂还延迟了自主活性的下降，且花萼海绵诱癌素A的作用比冈田酸更强。环孢菌素A是蛋白磷酸酶2B（PP2B）的抑制剂，没有作用。数据表明，PP1可能参与了CaMK II的去磷酸化以及自主活性的下降。
