Carboxyl Methylation of Ras-Related Proteins During Signal Transduction in Neutrophils

In human neutrophils, as in other cell types, Ras-related guanosine triphosphate-binding proteins are directed toward their regulatory targets in membranes by a series of posttrans-lational modifications that include methyl esterification of a carboxyl-terminal prenylcysteine residue. In intact cells and in a reconstituted in vitro system, the amount of carboxyl methylation of Ras-related proteins increased in response to the chemoattractant N-formylmethionyl-leucyl-phenylalanine (FMLP). Activation of Ras-related proteins by guanosine-5′-O-(3-thiotriphosphate) had a similar effect and induced translocation of p22$^{rac2}$ from cytosol to plasma membrane. Inhibitors of prenylcysteine carboxyl methylation effectively blocked neutrophil responses to FMLP. These findings suggest a direct link between receptor-mediated signal transduction and the carboxyl methylation of Ras-related proteins.