Effects of Newly Synthesized DCP-LA-Phospholipids on Protein Kinase C and Protein Phosphatases
Effects of Newly Synthesized DCP-LA-Phospholipids on Protein Kinase C and Protein Phosphatases
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DOI：
10.1159/000350076
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发表时间：
2013-01-01
影响因子：
--
通讯作者：
Nishizaki, Tomoyuki
中科院分区：
文献类型：
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作者：
Kanno, Takeshi;Tsuchiya, Ayako;Nishizaki, Tomoyuki
背景/目的：亚油酸衍生物DCP-LA选择性地激活PKC epsilon并抑制蛋白磷酸酶1(PP1)。在本研究中，我们合成了α、β位含DCP-LA的磷脂酰乙醇胺、-丝氨酸、-胆碱和-肌醇(分别为diDCP-LA-PE、-PS、PC和-PI)，并研究了这些化合物对PKC同工酶和蛋白磷酸酶活性的影响。方法：在无细胞条件下测定PKC同工酶PKCα、-βI、-βII、-γ、-epsilon、-IOTA、…和-Zeta的活性以及蛋白磷酸酶PP1、PP2A和蛋白酪氨酸磷酸酶1B(PTP1B)的活性。结果：所有化合物均激活PKC，但diDCP-LA-PC仅对PKC有伽马抑制作用。化合物diDCP-LA-PE单独对PKC和-Zeta有明显的激活作用。DiDCP-LA-PE和diDCP-LA-PI抑制PP1活性，而diDCP-LA-PI增强PP2A活性。DiDCP-LA-PE、diDCP-LA-PS和diDCP-LA-PI显著降低PTP1B活性，而diDCP-LA-PC增强PTP1B活性。结论：所有新合成的DCPLA-磷脂都是PKC激活剂，其中diDCP-LA-PE单独具有激活非典型PKC同工酶PKC iota和-Zeta的潜力。DiDCP-LA-PE和diDCP-LA-PI是PP1和PTP1B的抑制剂，diDCP-LA-PS是PTP1B的抑制剂，diDCP-LA-PI是PP2A的增强剂，diDCP-LA-PC是PTP1B的增强剂。版权所有(C)2013 S.Karger AG，巴塞尔
Background/Aims: The linoleic acid derivative DCP-LA selectively activates PKC epsilon and inhibits protein phosphatase 1 (PP1). In the present study, we have newly synthesized phosphatidyl-ethanolamine, -serine, -choline, and -inositol containing DCP-LA at the alpha and beta position (diDCP-LA-PE, -PS, PC, and -PI, respectively), and examined the effects of these compounds on activities of PKC isozymes and protein phosphatases. Methods: Activities of PKC isozymes PKC alpha, -beta I, -beta II, -gamma, -epsilon, -iota,., and -zeta and protein phosphatases PP1, PP2A, and protein tyrosine phosphatase 1B (PTP1B) were assayed under the cell-free conditions. Results: All the compounds activated PKC, with the different potential, but only PKC gamma inhibition was obtained with diDCP-LA-PC. Of compounds diDCP-LA-PE alone significantly activated PKC iota and -zeta. diDCP-LA-PE and diDCP-LA-PI suppressed PP1 activity, but otherwise diDCP-LA-PI enhanced PP2A activity. diDCP-LA-PE, diDCP-LA-PS, and diDCP-LA-PI strongly reduced PTP1B activity, while diDCP-LA-PC enhanced the activity. Conclusion: All the newly synthesized DCPLA- phospholipids serve as a PKC activator and of them diDCP-LA-PE alone has the potential to activate the atypical PKC isozymes PKC iota and -zeta. diDCP-LA-PE and diDCP-LA-PI serve as an inhibitor for PP1 and PTP1B, diDCP-LA-PS as a PTP1B inhibitor, diDCP-LA-PI as a PP2A enhancer, and diDCP-LA-PC as a PTP1B enhancer. Copyright (C) 2013 S. Karger AG, Basel