Effects of farnesylcysteine analogs on protein carboxyl methylation and signal transduction.
Several proteins associated with signal transduction in eukaryotes are carboxyl methylated at COOH-terminal S-farnesylcysteine residues. These include members of the Ras superfamily and gamma-subunits of heterotrimeric G-proteins. The enzymes that catalyze the carboxyl methylation reaction also methylate small molecules such as N-acetyl-S-trans, trans-farnesyl-L-cysteine (AFC). AFC inhibits carboxyl methylation of p21ras and related proteins both in vitro and in vivo. Saturating concentrations of AFC cause a greater than 80% inhibition of chemotactic responses of mouse peritoneal macrophages. Our results suggest that carboxyl methylation may play a role in the regulation of receptor-mediated signal transduction processes in eukaryotic cells.
Department of Molecular Biology, Princeton University, New Jersey 08544-1014.
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Volker
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Miller
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McCleary
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Rao
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Poenie
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Backer
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D019883:Alkyl and Aryl Transferases; D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002633:Chemotaxis / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D046911:Macromolecular Substances; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009928:Organ Specificity; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014166:Transferases / Q000378:metabolism*
D046911:Macromolecular Substances; C057785:S-farnesylcysteine; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras); D003545:Cysteine