Jefferson A B, Schulman H
Department of Pharmacology, Stanford University School of Medicine, California 94305-5332.
J Biol Chem. 1988 Oct 25;263(30):15241-4.
Sphingosine is a potent inhibitor of several calmodulin-dependent enzymes. The multifunctional Ca2+/calmodulin-dependent protein kinase, a Ca2+/calmodulin-dependent phosphodiesterase, and smooth muscle myosin light chain kinase are inhibited in vitro at concentrations previously shown to inhibit protein kinase C. Inhibition of each of the enzymes is competitive with calmodulin, suggesting that sphingosine may be a calmodulin antagonist. In the pituitary cell line GH3, sphingosine inhibits the phosphorylation of microtubule-associated protein 2 by the multifunctional Ca2+/calmodulin-dependent protein kinase and the phosphorylation of elongation factor 2 by Ca2+/calmodulin-dependent kinase III. These findings suggest that sphingosine, in blocking the effects of both the Ca2+.calmodulin complex and of diacylglycerol, may be a very effective inhibitor of both branches of the phosphatidylinositol signaling pathway. By extension, caution should be exercised in the use of sphingosine as a diagnostic test for the involvement of protein kinase C in biological processes.
鞘氨醇是几种钙调蛋白依赖性酶的有效抑制剂。多功能Ca2+/钙调蛋白依赖性蛋白激酶、一种Ca2+/钙调蛋白依赖性磷酸二酯酶和平滑肌肌球蛋白轻链激酶在体外被抑制，其浓度先前已显示可抑制蛋白激酶C。每种酶的抑制作用与钙调蛋白具有竞争性，这表明鞘氨醇可能是一种钙调蛋白拮抗剂。在垂体细胞系GH3中，鞘氨醇抑制多功能Ca2+/钙调蛋白依赖性蛋白激酶对微管相关蛋白2的磷酸化以及Ca2+/钙调蛋白依赖性激酶III对延伸因子2的磷酸化。这些发现表明，鞘氨醇在阻断Ca2+·钙调蛋白复合物和二酰基甘油的作用时，可能是磷脂酰肌醇信号通路两个分支的非常有效的抑制剂。由此推论，在将鞘氨醇用作蛋白激酶C参与生物过程的诊断测试时应谨慎。
