Activation-dependent carboxyl methylation of neutrophil G-protein γ subunit

M. R. Philips, R. Staud, M. Pillinger, A. Feoktistov, C. Volker, J. B. Stock, G. Weissmann

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34 Scopus citations


The γ subunits of heterotrimeric guanine nucleotide-binding regulatory (G) proteins (G(γ)) are post-translationally processed at their C termini by prenylation, proteolysis, and carboxyl methylation. Whereas prenylation of G(γ), is required for membrane association of G proteins, the role of carboxyl methylation is unknown. Here we show that human neutrophils express G(γ2) but not G(γ3) or G(γ7) and that carboxyl methylation of G(γ2) is associated with signal transduction. In a reconstituted cell-free system, neutrophil was labeled by the methyl donor S-[methyl-3H]adenosyl-L- methionine. Carboxyl methylation was confirmed by alkaline hydrolysis and quantitation of volatile [3H]methanol. Neutrophil G(γ2) methylation was stimulated by activation of G protein with guanosine 5'-[β,γ- thio]triphosphate. We estimate that after 1 hr of G-protein activation at least 6% of the total pool of G(γ2) was carboxyl-methylated. The inflammatory agonist fMet-Leu-Phe stimulated guanosine 5'-[β,γ- thio]triphosphate-dependent carboxyl methylation. Methylation of G(γ2) was inhibited by the carboxyl methyltransferase inhibitor N-acetyl-S- trans,trans-farnesylcysteine at concentrations that affected signal transduction in neutrophils. These results demonstrate that activation of neutrophil G(i) is associated with α-carboxyl methyl esterification of G(γ2) and suggest that carboxyl methylation of G(γ) may play a role in signal transduction.

Original languageEnglish (US)
Pages (from-to)2283-2287
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number6
StatePublished - 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


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