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.
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.
Feng
W
W
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Song
Z H
ZH
D000262:Adenylyl Cyclases / Q000378:metabolism*; D020816:Amino Acid Motifs; D002186:Cannabinoids / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D016296:Mutagenesis; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000737:chemistry* / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
D002186:Cannabinoids; D008024:Ligands; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D014443:Tyrosine; D000262:Adenylyl Cyclases; D003545:Cysteine