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 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.
Philips
M R
MR
Department of Medicine, New York University Medical Center, NY 10016.
Pillinger
M H
MH
Staud
R
R
Volker
C
C
Rosenfeld
M G
MG
Weissmann
G
G
Stock
J B
JB
D002462:Cell Membrane / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D008745:Methylation; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011496:Protein Methyltransferases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014316:Tritium; D020668:rap GTP-Binding Proteins; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D020730:Guanine Nucleotide Dissociation Inhibitors; D011518:Proto-Oncogene Proteins; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D014316:Tritium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009240:N-Formylmethionine Leucyl-Phenylalanine; D012436:S-Adenosylmethionine; D006160:Guanosine Triphosphate; D008715:Methionine; C038344:methionine methyl ester; D011496:Protein Methyltransferases; C056501:protein-S-isoprenylcysteine O-methyltransferase; D019204:GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D020668:rap GTP-Binding Proteins