Phospholipid-binding protein domains.

Abstract

Research into cellular mechanisms for signal transduction is currently one of the most exciting and rapidly advancing fields of biological study. It has been known for some time that numerous intracellular signals are transmitted by specific protein-protein interactions, as exemplified by those involving the Src homology domains. However, after some controversy, it has recently been widely accepted that specific protein-phospholipid interactions also play key roles in many signal transduction pathways. In this review, landmark 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 messengers in signalling pathways. For this purpose, the pleckstrin homology (PH) domain is highlighted, since studies of this domain provided some of the earliest, detailed data about protein-phospholipid interactions occurring downstream of growth factor-mediated receptor stimulation. Moreover, studies of PH domains have given insight into the mechanisms of certain diseases, revealed a number of intriguing functional variations on a common structural theme and recently culminated in providing the missing links in erstwhile mysteries of phosphoinositide-dependent signal transduction pathways. Finally, a short discussion is devoted to the developing field of protein-phospholipid interactions that influence cytoskeletal organisation.