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Chemoattractant receptor-specific differences in G protein activation rates regulate effector enzyme and functional responses.

A A Jacobs·J L Huber·R A Ward·J B Klein·K R McLeish
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Abstract

The hypothesis that disparate neutrophil functional responses to various chemoattractants are regulated by receptor-specific rates of G protein activation was examined in HL-60 granulocytes. The initial rates of G protein activation and the affinity of receptor-stimulated G proteins for GTP gamma S in HL-60 membranes stimulated by fMet-Leu-Phe, C5a, and leukotriene B4 (LTB4) differed significantly among the chemoattractants, with a rank order of fMet-Leu-Phe > C5a > LTB4. Equilibrium GTP gamma S binding showed that all three chemoattractants activated a common pool of G proteins. Stimulation of phospholipase D activation, measured as phosphatidylethanol generation, and superoxide release in intact cells also occurred with a rank order of fMet-Leu-Phe > C5a > LTB4. On the other hand, the rank order of receptor affinities for ligand and of the EC50 of chemoattractant stimulation of GTP gamma S binding was C5a > LTB4 > fMet-Leu-Phe. C5a and LTB4 receptor densities were similar but were less than formyl peptide receptor density. Graded pertussis toxin treatment proportionally reduced superoxide release and phospholipase D activation to all three chemoattractants. The results suggest that receptor-specific differences in G protein affinity for guanine nucleotides lead to different rates of guanine nucleotide exchange and, thereby, contribute to disparate effector enzyme and functional responses.

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Amino Acid SequenceChemotactic FactorsEnzyme ActivationGTP-Binding ProteinsGranulocytesGuanosine 5'-O-(3-Thiotriphosphate)HumansKineticsLeukemia, MyeloidMolecular Sequence DataN-Formylmethionine Leucyl-PhenylalaninePhospholipase DReceptors, Formyl PeptideReceptors, ImmunologicReceptors, PeptideStimulation, ChemicalSubstrate SpecificityComparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.

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A A Jacobs, J L Huber, R A Ward, J B Klein, K R McLeish. 1995. Chemoattractant receptor-specific differences in G protein activation rates regulate effector enzyme and functional responses.. https://doi.org/10.1002/jlb.57.4.679

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