Role of the highly conserved Asp-Arg-Tyr motif in signal transduction of the CB2 cannabinoid receptor.
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.
Rhee
M H
MH
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
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Levy
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Vogel
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D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D017124:Conserved Sequence; D017931:DNA Primers; D008024:Ligands; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D017931:DNA Primers; D008024:Ligands; D009842:Oligopeptides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug