Understanding of the roles of phospholipase D and phosphatidic acid through their binding partners.

Abstract Phospholipase D (PLD) is a phosphatidyl choline (PC)-hydrolyzing enzyme that generates phosphatidic acid (PA), a lipid second messenger that modulates diverse intracellular signaling. Through interactions with signaling molecules, both PLD and PA can mediate a variety of cellular functions, such as, growth/proliferation, vesicle trafficking, cytoskeleton modulation, development, and morphogenesis. Therefore, systemic approaches for investigating PLD networks including interrelationship between PLD and PA and theirs binding partners, such as proteins and lipids, can enhance fundamental knowledge of roles of PLD and PA in diverse biological processes. In this review, we summarize previously reported protein–protein and protein–lipid interactions of PLD and PA and their binding partners. In addition, we describe the functional roles played by PLD and PA in these interactions, and provide PLD network that summarizes these interactions. The PLD network suggests that PLD and PA could act as a decision maker and/or as a coordinator of signal dynamics. This viewpoint provides a turning point for understanding the roles of PLD–PA as a dynamic signaling hub.