ADP-ribosylation factor-dependent phospholipase D activation by the M-3 muscarinic receptor

R. Mitchell, D.N. Robertson, P.J. Holland, D. Collins, E.M. Lutz, M.S. Johnson

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 Gq/11, phospholipase C, Ca2, 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.
Original languageEnglish
Pages (from-to)33818-33830
Number of pages12
JournalJournal of Biological Chemistry
Volume278
Issue number36
DOIs
Publication statusPublished - 5 Sep 2003

Keywords

  • ADP-ribosylation
  • phospholipase D
  • M-3 muscarinic receptor

Fingerprint Dive into the research topics of 'ADP-ribosylation factor-dependent phospholipase D activation by the M-3 muscarinic receptor'. Together they form a unique fingerprint.

Cite this