Role of carboxylmethylation in chemoattractant receptor-stimulated G protein activation and functional responses

The role of G protein γ subunit carboxylmethylation was examined in HL-60 granulocytes using an inhibitor of S-adenosylmethionine-dependent methylation, periodate-oxidized adenosine (Adox). A 40-60% reduction in γ subunit carboxylmethylation was associated with attenuation of fMet-Leu-Phe-stimulated GTPγS binding and GTP hydrolysis, while plasma membrane density of formyl peptide receptors, α(i)2, α(i)3, β, γ₅, and γ₇ were not reduced. Reduced pertussis toxin-catalyzed ADP-ribosylation was re-established by in vitro methylation or addition of transducin βγ subunits. Superoxide release and inositol phosphate generation stimulated by fMet-Leu-Phe were significantly inhibited by Adox treatment. Carboxylmethylation contributes to transmembrane signalling and functional responses by enhancing association of α and βγ subunits.