Long-Chain Fatty Acylation of Proteins

Reversible modifications of cellular proteins often serve as key steps in signal transduction and effector pathways, and the investigation of these modifications has been a principal route of access to signaling mechanisms. Ten years ago, for example, tyrosine phosphorylation was an intriguing oddity—a posttranslational modification known to occur in virtually all eukaryotic cells and to be regulated by various manipulations that alter cell growth or differentiation, but with no clear physiological role. From the elucidation of tyrosine kinase pathways emerged a dramatically new view of how cells transduce and integrate signaling cascades controlling cellular functions from growth to death (see Chapter 6). Today, another dynamic posttranslational modification—the covalent attachment of palmitate or other longchain fatty acids to cysteine residues (Schmidt, 1989; James and Olson, 1990)—is coming to be recognized as an important component of signal transduction pathways. Like tyrosine phosphorylation a decade ago, S-palmitoylation today is known to occur in all eukaryotic cells and to be regulated by a variety of signals that alter cell growth, metabolism, or repair (Huang, 1989; James and Olson, 1989; Mouillac et al., 1992; Hess et al., 1993; Wedegaertner and Bourne, 1994; Robinson et al., 1995).