Association of the N-formyl-Met-Leu-Phe receptor in human neutrophils with a GTP-binding protein sensitive to pertussis toxin.
Pertussis toxin inhibits the N-formyl-Met-Leu-Phe (fMet-Leu-Phe) mediated human neutrophil functions of enzyme release, superoxide generation, aggregation, and chemotaxis. As pertussis toxin modifies the GTP binding receptor-regulatory protein "Ni," the association of the fMet-Leu-Phe receptor with such a protein was further examined in purified neutrophil plasma membranes. Both fMet-Leu-Phe-mediated guanine nucleotide exchange and nucleotide-mediated regulation of the fMet-Leu-Phe receptor are inhibited by pertussis toxin. In addition, membrane pretreatment with pertussis toxin abolishes the fMet-Leu-Phe-mediated inhibition of adenylate cyclase. Actions of pertussis toxin are due to the ADP-ribosylation of a single subunit at 41 kDa in the neutrophil plasma membrane, which comigrates on NaDodSO4 gels with the Ni GTP-binding protein in the platelet plasma membrane. Our results suggest that (i) the fMet-Leu-Phe receptor is associated with a Ni GTP regulatory protein, and (ii) a fMet-Leu-Phe-Ni complex is important in the control of several neutrophil functions, probably involving multiple transduction systems, including adenylate cyclase.
Lad
P M
PM
Olson
C V
CV
Smiley
P A
PA
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D001427:Bacterial Toxins / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors; D009243:NAD / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism*; D037342:Pertussis Toxin; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D010566:Virulence Factors, Bordetella
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D001427:Bacterial Toxins; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D010566:Virulence Factors, Bordetella; D009243:NAD; D013481:Superoxides; D006165:Guanylyl Imidodiphosphate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins