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J Biol Chem. 2003 Sep 5;278(36):33818-30. Epub 2003 Jun 10.

ADP-ribosylation factor-dependent phospholipase D activation by the M3 muscarinic receptor.

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  • 1Medical Research Council Membrane and Adapter Proteins Co-operative Group, Membrane Biology Interdisciplinary Research Group, School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, EH8 9XD, United Kingdom. Rory.Mitchell@ed.ac.uk

Abstract

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.

PMID:
12799371
[PubMed - indexed for MEDLINE]
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