Role of carboxylmethylation in chemoattractant receptor-stimulated G protein activation and functional responses.
The role of G protein gamma 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 gamma subunit carboxyl-methylation was associated with attenuation of fMet-Leu-Phe-stimulated GTP gamma S binding and GTP hydrolysis, while plasma membrane density of formyl peptide receptors, alpha i2, alpha i3, beta, gamma 5, and gamma 7 were not reduced. Reduced pertussis toxin-catalyzed ADP-ribosylation was re-established by in vitro methylation or addition of transducin beta gamma 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 alpha and beta gamma subunits.
Lederer
E D
ED
Department of Biochemistry, University of Louisville School of Medicine, KY.
Jacobs
A A
AA
Hoffman
J L
JL
Harding
G B
GB
Robishaw
J D
JD
McLeish
K R
KR
D000241:Adenosine / Q000737:chemistry; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D010084:Oxidation-Reduction; D010504:Periodic Acid / Q000737:chemistry; D037342:Pertussis Toxin; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D010566:Virulence Factors, Bordetella; D010504:Periodic Acid; D013481:Superoxides; D000246:Adenosine Diphosphate Ribose; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012436:S-Adenosylmethionine; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000241:Adenosine