Role of the highly conserved Asp-Arg-Tyr motif in signal transduction of the CB2 cannabinoid receptor

FEBS Lett. 2000 Jan 28;466(2-3):300-4. doi: 10.1016/s0014-5793(00)01094-2.


The DRY motif, at the junction of transmembrane helix 3 and intracellular loop 2 of G protein-coupled receptors, is highly conserved. Mutations were introduced into the CB2 cannabinoid receptor to study the role of this motif in CB2 signaling. D mutations (DRY130-132AAA and D130A) markedly reduced binding of cannabinoid agonists, while no significant reduction was observed with R131A or Y132A. Mutating R (R131A) only partially reduced, and mutating Y (Y132A) more efficiently reduced the cannabinoid-induced inhibition of adenylyl cyclase. Thus, in CB2, D130 is involved in agonist binding, whereas Y seems to have a role in receptor downstream signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • COS Cells
  • Conserved Sequence
  • DNA Primers
  • Ligands
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Protein Binding
  • Receptors, Cannabinoid
  • Receptors, Drug / agonists
  • Receptors, Drug / chemistry
  • Receptors, Drug / metabolism*
  • Signal Transduction*


  • DNA Primers
  • Ligands
  • Oligopeptides
  • Receptors, Cannabinoid
  • Receptors, Drug