Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Membrane / metabolism
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Cytosol / metabolism
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GTP-Binding Proteins / metabolism*
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Guanine Nucleotide Dissociation Inhibitors*
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Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
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Guanosine Triphosphate / pharmacology
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Humans
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Methionine / analogs & derivatives
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Methionine / metabolism
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Methylation
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N-Formylmethionine Leucyl-Phenylalanine / pharmacology
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Neutrophils / physiology*
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Protein Methyltransferases / metabolism
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins p21(ras) / metabolism
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S-Adenosylmethionine / metabolism
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Signal Transduction / physiology*
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Tritium
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rap GTP-Binding Proteins
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rho-Specific Guanine Nucleotide Dissociation Inhibitors
Substances
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Guanine Nucleotide Dissociation Inhibitors
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Proto-Oncogene Proteins
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rho-Specific Guanine Nucleotide Dissociation Inhibitors
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Tritium
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Guanosine 5'-O-(3-Thiotriphosphate)
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N-Formylmethionine Leucyl-Phenylalanine
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S-Adenosylmethionine
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Guanosine Triphosphate
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Methionine
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methionine methyl ester
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Protein Methyltransferases
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protein-S-isoprenylcysteine O-methyltransferase
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GTP-Binding Proteins
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)
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rap GTP-Binding Proteins