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

• Published in: Science (American Association for the Advancement of Science) 1993-02, Vol.259 (5097), p.977-980
• Main Authors: Philips, Mark R., Pillinger, Michael H., Staud, Roland, Volker, Craig, Rosenfeld, Melvin G., Weissmann, Gerald, Stock, Jeffry B.
• Format: Article
• Language: English
• Subjects: activation; Automatic frequency control; Average fixed cost; Biological and medical sciences; Cell Membrane - metabolism; Cell membranes; Cell physiology; Cellular signal transduction; chemoattractants; Cytosol; Cytosol - metabolism; Fundamental and applied biological sciences. Psychology; GTP-Binding Proteins - metabolism; Guanine Nucleotide Dissociation Inhibitors; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology; Guanosine Triphosphate - pharmacology; Humans; leukocytes (neutrophilic); man; Methionine - analogs & derivatives; Methionine - metabolism; Methylation; Molecular and cellular biology; N-formyl-methionyl-leucyl-phenylalanine; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils; Neutrophils - physiology; P branes; Plasma membranes; Protein Methyltransferases - metabolism; Proteins; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins p21(ras) - metabolism; rap GTP-Binding Proteins; ras-related protein; rho-Specific Guanine Nucleotide Dissociation Inhibitors; S-Adenosylmethionine - metabolism; Signal transduction; Signal Transduction - physiology; String theory; Tritium
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8438158

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.