guanosine-triphosphate and methionine-methyl-ester

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 posttranslational 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-formyl-methionyl-leucyl-phenylalanine (FMLP). Activation of Ras-related proteins by guanosine-5'-O-(3-thiotriphosphate) had a similar effect and induced translocation of p22rac2 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.

Topics: Cell Membrane; Cytosol; GTP-Binding Proteins; Guanine Nucleotide Dissociation Inhibitors; Guanosine 5'-O-(3-Thiotriphosphate); Guanosine Triphosphate; Humans; Methionine; Methylation; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Protein Methyltransferases; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); rap GTP-Binding Proteins; rho-Specific Guanine Nucleotide Dissociation Inhibitors; S-Adenosylmethionine; Signal Transduction; Tritium