Signalling roles of mammalian phospholipase D1 and D2

Phospholipase D (PLD) catalyses the hydrolysis of phosphatidylcholine to ge nerate the lipid second messenger, phosphatidate (PA) and choline. PLD acti vity in mammalian cells is low and is transiently stimulated upon activatio n by G-protein-coupled and receptor tyrosine kinase cell surface receptors. Two mammalian PLD enzymes (PLD1 and PLD2) have been cloned and their intra cellular regulators identified as ARF and Rho proteins, protein kinase Ca a s well as the lipid, phosphatidylinositol [4, 5] bisphosphate (PIP,). I dis cuss the regulation of these enzymes by cell surface receptors, their cellu lar localisation and the potential function of PA as a second messenger. Ev idence is presented for a role of PA in regulating the lipid kinase activit y of PIP 5-kinase, an enzyme that synthesises PIP,. A signalling role of ph ospholipase D via PA and indirectly via PIP, in regulating membrane traffic and actin dynamics is indicated by the available data.