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

Mark R. Philips, Roland Staud, Michael Pillinger, Aleksander Feoktistov, Craig Volker, Juffry B. Stock, Gerald Weissmann

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34 Scopus citations


The γ subunits of heterotrimeric guanine nucleotide-binding regulatory (G) proteins (Gγ) are posttranslationally processed at their C termini by prenylation, proteolysis, and carboxyl methylation. Whereas prenylation of Gγ is required for membrane association of G proteins, the role of carboxyl methylation is unknown. Here we show that human neutrophils express Gγ2 but not Gγ3 or Gγ7 and that carboxyl methylation of Gγ2 is associated with signal transduction. In a reconstituted cell-free system, neutrophil Gγ2 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 Gγ2 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 Gγ2 was carboxyl-methylated. The inflammatory agonist fMet-Leu-Phe stimulated guanosine 5′-[β,γ-thio]triphosphate-dependent carboxyl methylation. Methylation of Gγ2 was inhibited by the carboxyl methyltransferase inhibitor N-acetyl-S-trans,fransesylcysteine at concentrations that affected signal transduction in neutrophils. These results demonstrate that activation of neutrophil Gi is associated with α-carboxyl methyl esterification of Gγ2 and suggest that carboxyl methylation of Gγ 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 - Mar 14 1995

All Science Journal Classification (ASJC) codes

  • General


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