Posttranslational protein palmitoylation: promoting platelet purpose.

Posttranslational modification of proteins is the foundation of intracellular signaling. Without the ability to reversibly modify proteins and lipids, cells would be unable to react to signals received from their environment. Posttranslational modification of proteins usually, but not always, occurs after a protein has arrived at the appropriate subcellular location. In certain instances, however, such modifications serve as addresses to correctly target the protein within the cell. See page 1478 Phosphorylation is the most widely studied of the posttranslational modifications. Both proteins and lipids can be reversibly phosphorylated, with the modification thereby being able to act as an on/off switch for the propagation of intracellular signals. Proteins can also be modified by attachment of lipid moieties (lipidation), modifications which have in recent years gained attention for their significant roles in propagating intracellular signals. Lipid modifications of proteins fall into several categories, of which 4 are predominant: (1) N-myristoylation, where myristate (C14) is cotranslationally attached to proteins at N-terminal glycine residues1–3; (2) Addition of glycosyl phosphatidylinositol (GPI) anchors, where GPI is attached to the C termini of proteins4; (3) S-prenylation, where a farnesyl (C15) or geranylgeranyl (C20) moiety is attached to a C-terminal cysteine within a CAAX motif (where C is cysteine, A is an aliphatic amino acid, and X is any amino acid)5; and (4) S-acylation (also known as S-palmitoylation) where palmitate (C16) and, less frequently, other fatty acids are attached to cysteine residues.6,7 Of the known membrane-targeting lipid modifications, palmitoylation is unique in two respects: (1) cysteinyl residues to be palmitoylated are not specified by obvious consensus sequences6 and (2) the process is reversible,8,9 which renders palmitoylation/depalmitoylation capable of regulating cellular functions. Further, although palmitate is the preferred acyl chain transferred to proteins by the palmitoyl …

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