Regulation of phospholipase D
Regulation of phospholipase D
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DOI：
10.1016/s0014-5793(02)03405-1
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发表时间：
2002-10-30
期刊：
影响因子：
3.5
通讯作者：
Exton, JH
中科院分区：
文献类型：
--
作者：
Exton, JH
对磷脂酶D(PLD)超家族中植物和细菌成员的结构研究提供了关于保守的HKD结构域在催化中心结构中的作用以及哺乳动物PLD同工酶(PLD1和PLD2)的催化机制的信息。突变和序列比较研究也确定了N-末端存在pleckstrin同源结构域和Phox同源结构域，并证明了C-末端的保守序列是催化所必需的。PLD1的N-末端和C-末端还含有蛋白激酶C的相互作用部位，可以通过非磷酸化机制直接激活该酶。Rho和ADP-核糖化因子家族的小G蛋白也直接调节酶，RhoA与C末端的序列结合。某些酪氨酸激酶和小G蛋白的Ras亚家族成员可以激活该酶，但其机制似乎是间接的。激动剂在体内激活PLD的机制可能涉及多种途径。(C)2002年欧洲生化学会联合会。爱思唯尔科学公司出版。版权所有。
Structural studies of plant and bacterial members of the phospholipase D (PLD) superfamily are providing information about the role of the conserved HKD domains in the structure of the catalytic center and the catalytic mechanism of mammalian PLD isozymes (PLD1 and PLD2). Mutagenesis and sequence comparison studies have also defined the presence of pleckstrin homology and phox homology domains in the N-terminus and have demonstrated that a conserved sequence at the C-terminus is required for catalysis. The N- and C-terminal regions of PLD1 also contain interaction sites for protein kinase C, which can directly activate the enzyme through a nonphosphorylating mechanism. Small G proteins of the Rho and ADP-ribosylation factor families also directly regulate the enzyme, with RhoA binding to a sequence in the C-terminus. Certain tyrosine kinases and members of the Ras subfamily of small G proteins can activate the enzyme, but the mechanisms appear to be indirect. The mechanisms by which agonists activate PLD in vivo probably involve multiple pathways.(C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.