Phospholipid-binding protein domains

Research into cellular mechanisms for signal transduction is currently one of the most exciting and rapidly advancing fields of biological study. It h as been known for some time that numerous intracellular signals are transmi tted by specific protein-protein interactions, as exemplified by those invo lving the Src homology domains. However, after some controversy, it has rec ently been widely accepted that specific protein-phospholipid interactions also play key roles in many signal transduction pathways. In this review, l andmark discoveries and recent advances describing protein domains known to associate with phospholipids are discussed. Particular emphasis is placed on the interactions of proteins with phospholipids acting as second messeng ers in signalling pathways. For this purpose, the pleckstrin homology (PH) domain is highlighted, since studies of this domain provided some of the ea rliest, detailed data about protein-phospholipid interactions occurring dow nstream of growth factor-mediated receptor stimulation. Moreover, studies o f PH domains have given insight into the mechanisms of certain diseases, re vealed a number of intriguing functional variations on a common structural theme and recently culminated in providing the missing links in erstwhile m ysteries of phosphoinositide-dependent signal transduction pathways. Finall y, a short discussion is devoted to the developing field of protein-phospho lipid interactions that influence cytoskeletal organisation. (C) 1998 Elsev ier Science B.V. All rights reserved.