Functional roles of the tyrosine within the NP(X)(n)Y motif and the cysteines in the C-terminal juxtamembrane region of the CB2 cannabinoid receptor

FEBS Lett. 2001 Jul 20;501(2-3):166-70. doi: 10.1016/s0014-5793(01)02642-4.


In G protein-coupled receptors, a NP(X)(n)Y motif in the seventh transmembrane domain and cysteine residues in the C-terminal juxtamembrane region are conserved. In the current study, the roles of Y299 within the NPVIY motif and C313 and C320 in the C-terminal juxtamembrane region of the human CB2 cannabinoid receptor were investigated by site-directed mutagenesis. Replacing Y299 with alanine resulted in a complete loss of ligand binding and a severe impairment of cannabinoid-induced inhibition of forskolin-stimulated cAMP accumulation. The C313A and C320A mutations markedly reduced functional coupling to adenylate cyclase, but had no effect on ligand binding and agonist-induced receptor desensitization.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Amino Acid Motifs
  • Cannabinoids / metabolism
  • Cells, Cultured
  • Cysteine / chemistry
  • Cysteine / metabolism*
  • Humans
  • Ligands
  • Models, Molecular
  • Mutagenesis
  • Receptors, Cannabinoid
  • Receptors, Drug / chemistry*
  • Receptors, Drug / metabolism
  • Tyrosine / chemistry
  • Tyrosine / metabolism*


  • Cannabinoids
  • Ligands
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Tyrosine
  • Adenylyl Cyclases
  • Cysteine