Exton John H
Howard Hughes Medical Institute and Vanderbilt University Medical Center, Nashville, TN 38232-0295, USA.
FEBS Lett. 2002 Oct 30;531(1):58-61. doi: 10.1016/s0014-5793(02)03405-1.
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 non-phosphorylating 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.
磷脂酶D（PLD）超家族中植物和细菌成员的结构研究，正在提供有关保守的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）催化机制的信息。诱变和序列比较研究还确定了N端存在普列克底物蛋白同源结构域和吞噬细胞氧化酶同源结构域，并证明C端的保守序列是催化所必需的。PLD1的N端和C端区域还包含蛋白激酶C的相互作用位点，蛋白激酶C可通过非磷酸化机制直接激活该酶。Rho和ADP核糖基化因子家族的小G蛋白也直接调节该酶，RhoA与C端的一个序列结合。某些酪氨酸激酶和小G蛋白Ras亚家族的成员可以激活该酶，但机制似乎是间接的。体内激动剂激活PLD的机制可能涉及多种途径。
