title: Key amino acids for differential coupling of alpha1-adrenergic receptor subtypes to Gs.
abstract: We have established that differing effects of alpha1-adrenergic receptor (AR) subtypes on cell proliferation are due to differential coupling to the Gs/cAMP pathway; thus, both alpha1A- and alpha1B-ARs couple to Gs, while alpha1D-AR does not. To identify the region responsible for this difference in subtype-specific Gs coupling, we constructed a series of chimeric and a set of point-mutated human alpha1A- and alpha1D-ARs, and examined their signaling ability. Here, we show that the amino acid residues Thr 136 and Val138 in the intracellular loop II of the human alpha1A-AR are intimately involved with Gs coupling.
authors.affiliation: Department of Molecular, Cell Pharmacology, National Center for Child Health and Development Research Institute, 3-35-31 Taishido, Setagaya-Ku, 154-8509, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Shinoura
authors.forename: Katsushi
authors.initials: K
authors.lastname: Shibata
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D002455:Cell Division; D002462:Cell Membrane; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011869:Radioligand Assay; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D014162:Transfection; D014633:Valine / Q000378:metabolism
chemical_list: D000596:Amino Acids; D008024:Ligands; D018340:Receptors, Adrenergic, alpha-1; D013912:Threonine; D000242:Cyclic AMP; D014633:Valine