Key amino acids for differential coupling of alpha1-adrenergic receptor subtypes to Gs.
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.
Shinoura
Hitomi
H
Department of Molecular, Cell Pharmacology, National Center for Child Health and Development Research Institute, 3-35-31 Taishido, Setagaya-Ku, 154-8509, Tokyo, Japan.
Shibata
Katsushi
K
Hirasawa
Akira
A
Tanoue
Akito
A
Hashimoto
Keitaro
K
Tsujimoto
Gozoh
G
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
D000596:Amino Acids; D008024:Ligands; D018340:Receptors, Adrenergic, alpha-1; D013912:Threonine; D000242:Cyclic AMP; D014633:Valine