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首页> 外文期刊>Advances in enzyme regulation >Analysis of two diacylglycerol kinase activities in mixed micelles
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Analysis of two diacylglycerol kinase activities in mixed micelles

机译：混合胶束中两种二酰基甘油激酶活性的分析

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摘要

The number of signaling pathways modulated by lipid second messengers continues to grow. Two lipids that appear to play critical signaling roles are diacylglycerol (DAG) and phosphatidic acid (PA). Diacylglycerol kinases (DGKs, EC 2.7.1.107) catalyze the transfer of the y phosphate of ATP to the hydroxyl group of DAG to generate PA. Attention was first drawn to DGKs as this activity is important for phosphoinositide (PI) resynthesis within the PI cycle (Quest et al, 1996). DAG generated in this cycle is an allosteric activator of classic and novel calcium-insensitive protein kinase Cs (PKCs alpha, beta,gamma , delta, epsilon, eta, theta ). As DAG is the substrate for DGK, this enzyme has been implicated as an attenuator of PKC activity, thereby inactivating downstream signaling pathways (Nishizuka, 1992). In addition to PKC, however, DAG is also a key player in other cellular processes including a nuclear PIP kinase, regulators of small molecular weight G-proteins such as Ras (ras), and a protein involved in exocytosis (Muncl3) (Kazanietz, 2000). These additional DAG-binding proteins have highlighted the vital signaling role of this lipid. Importantly, the product of DGK, PA, is also an activator of some signaling enzymes such as Raf-1 kinase, PKC-zeta, and the protein tyrosine-phosphatase, PTP1C, and has been implicated in the stimulation of DNA synthesis (Ghosh et al., 1996; Limatola et al., 1994; Zhao et al., 1993). These data indicate that DGKs are exquisitely poised to modulate the relative level of two lipid second messengers, thereby placing them in an excellent position to coordinately regulate a number of signaling pathways.
机译：由脂质第二信使调节的信号传导途径的数目持续增长。似乎起关键信号作用的两种脂质是二酰基甘油（DAG）和磷脂酸（PA）。二酰基甘油激酶（DGKs，EC 2.7.1.107）催化ATP的y磷酸转移至DAG的羟基以生成PA。首先要注意DGK，因为该活性对于PI周期内的磷酸肌醇（PI）重新合成很重要（Quest等，1996）。在此循环中产生的DAG是经典和新型钙不敏感性蛋白激酶Cs（PKCs alpha，β，γ，δ，ε，η，θ）的变构激活剂。由于DAG是DGK的底物，因此该酶被认为是PKC活性的减弱剂，从而使下游的信号通路失活（Nishizuka，1992）。但是，除了PKC外，DAG还是其他细胞过程的关键参与者，包括核PIP激酶，小分子量G蛋白（例如Ras（ras））和参与胞吐作用的蛋白（Muncl3）（Kazanietz， 2000）。这些额外的DAG结合蛋白突显了这种脂质的重要信号传导作用。重要的是，宾夕法尼亚州DGK的产品还是某些信号酶（例如Raf-1激酶，PKC-zeta和酪氨酸磷酸酶PTP1C）的激活剂，并已参与了DNA合成的刺激（Ghosh等等人，1996; Limatola等，1994; Zhao等，1993）。这些数据表明，DGK的位置非常精确，可以调节两个脂质秒信使的相对水平，从而将它们置于一个出色的位置，可以协调地调节许多信号通路。

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