ADP-ribosylation factor-dependent phospholipase D activation by the M3 muscarinic receptor.
G protein-coupled receptors can potentially activate phospholipase D (PLD) by a number of routes. We show here that the native M3 muscarinic receptor in 1321N1 cells and an epitope-tagged M3 receptor expressed in COS7 cells substantially utilize an ADP-ribosylation factor (ARF)-dependent route of PLD activation. This pathway is activated at ... the plasma membrane but appears to be largely independent of G, phospholipase C, Ca2+ q/11, protein kinase C, tyrosine kinases, and phosphatidyl inositol 3-kinase. We report instead that it involves physical association of ARF with the M3 receptor as demonstrated by co-immunoprecipitation and by in vitro interaction with a glutathione S-transferase fusion protein of the receptor's third intracellular loop domain. Experiments with mutant constructs of ARF1/6 and PLD1/2 indicate that the M3 receptor displays a major ARF1-dependent route of PLD1 activation with an additional ARF6-dependent pathway to PLD1 or PLD2. Examples of other G protein-coupled receptors assessed in comparison display alternative pathways of protein kinase C- or ARF6-dependent activation of PLD2.
Mesh Terms:
ADP-Ribosylation Factor 1, ADP-Ribosylation Factors, Animals, Biotinylation, Blotting, Western, Brefeldin A, COS Cells, Carbachol, Cell Line, Cell Membrane, Dose-Response Relationship, Drug, Enzyme Activation, Enzyme Inhibitors, Epitopes, Estrenes, Glutathione Transferase, Humans, Immunoblotting, Inhibitory Concentration 50, Ligands, Models, Biological, Mutation, Phospholipase D, Precipitin Tests, Protein Binding, Protein Kinase C, Protein Structure, Tertiary, Protein Transport, Pyrrolidinones, Receptor, Muscarinic M3, Receptors, Muscarinic, Signal Transduction, Subcellular Fractions, Time Factors, Transfection, Tumor Cells, Cultured
ADP-Ribosylation Factor 1, ADP-Ribosylation Factors, Animals, Biotinylation, Blotting, Western, Brefeldin A, COS Cells, Carbachol, Cell Line, Cell Membrane, Dose-Response Relationship, Drug, Enzyme Activation, Enzyme Inhibitors, Epitopes, Estrenes, Glutathione Transferase, Humans, Immunoblotting, Inhibitory Concentration 50, Ligands, Models, Biological, Mutation, Phospholipase D, Precipitin Tests, Protein Binding, Protein Kinase C, Protein Structure, Tertiary, Protein Transport, Pyrrolidinones, Receptor, Muscarinic M3, Receptors, Muscarinic, Signal Transduction, Subcellular Fractions, Time Factors, Transfection, Tumor Cells, Cultured
J. Biol. Chem.
Date: Sep. 05, 2003
PubMed ID: 12799371
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