The role of the DRY motif of human MC4R for receptor activation.
We constructed several mutant human MC4R cDNAs by site directed mutagenesis and expressed these receptors in COS-1 cells. The conserved DRY motif among GPCRs was mutated to generate eight mutants. While no MC4R ligand binding was detected in any of the mutants, one mutant, D146A, resulted in higher cAMP production in cells than the wild-type receptor without ligand stimulation.
Yamano
Yoshiaki
Y
Department of Biochemistry and Biotechnology, Faculty of Agriculture, Tottori University, Tottori, Japan. yyamano@muses.tottori-u.ac.jp
Kamon
Rio
R
Yoshimizu
Takao
T
Toda
Yoshihisa
Y
Oshida
Yuichi
Y
Chaki
Shigeyuki
S
Yoshioka
Masanobu
M
Morishima
Isao
I
D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D008024:Ligands; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D011485:Protein Binding; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D008024:Ligands; C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP