Regulation of Phospholipase D (PLD) Activation and Small GTP-Binding Proteins

Abstract

Phospholipase D (PLD) hydrolyses membrane phospholipids, especially phosphatidylcholine (PC) and produces phosphatidic acid (PA) and choline. PLD is rapidly stimulated by many extracellular signal molecules in a wide variety of cell types and its activity is regulated by several factors such as protein kinase C, protein tyrosine kinase, calium ion and GTP-binding proteins. The mechanism of of PLD activation has been becoming clear with the recent demonstration that small GTP-binding proteins are identified as regulatory factors for PLD activity. ADP-ribosylation factor (ARF) as a cytosolic factor of PLD activity appears to directly interact with PLD, leading to its activation. Thus there is considerable speculation that this effect might contribute to the well-known ability of ARF to regulate intracellar membrane traffic. The role of the Rho family including RhoA, Rac and CDC42Hs is also considered to regulate PLD activity. In cell-free system of some cell types, ARF and Rho proteins exert a synergistic on PLD activation. More recently, Ral also has been shown to act as a PLD activator downstream of Ras in v-Src transfected cells. The PLD activation mechanism involving small GTP-binding proteins is much more complex than expected. In this chapter, we summarise recent information regarding the role (s) of small GTP-binding proteins in regulation of PLD activity.