TY - JOUR
T1 - Amino acids 356-372 constitute a Gi-activator sequence of the α2-adrenergic receptor and have a Phe substitute in the G protein-activator sequence motif
AU - Ikezu, Tsuneya
AU - Okamoto, Takashi
AU - Ogata, Etsuro
AU - Nishimoto, Ikuo
N1 - Funding Information:
Acknowledgements: We especially thank Dr, Toshiaki Katada (Tokyo Institute ol'Technology) for his gift of G proteins. We also thank Drs. Akira Kikuchi and Yoshimi Takai (Kobe University) and Dr. Yujiro Haya,qli (Sunlry Biomedical Institute) for their technical advice; Mr. Yoshiomi and Mrs. Yumi Tamai (Society For Educational Aid to Traffic Orphans) for indispensable support; Atomic Research General Center (University of Tokyo) for the use of their facilities; and Mr. Shuji Matsada, Ms. Yasuko Homma, Ms. Misaki Nagashima (University of Tokyo), and Ms. Patricia Beckman for technical assistance. This work was support~ in part by grants fi'om the Ministry of Education, Science, and Culture of Japan, Teijin Institute lbr Biomedical Research, the Life Insurance Association of Japan, Napolex Corporation, the Japan Research Foundation for Clinical Pharmacol. ogy, the Sagawa Foundation for Promotion of Cancer Research, the Mochida Men~orial Foundation for Medical and Pharmaceutical Re. search, Arima Memorial Foundation for Medical Research, Japan Heart Foundation Research Grant for 1991, and Kudo Science Foundation.
PY - 1992/10/12
Y1 - 1992/10/12
N2 - The human α2-adrenergic receptor contains the sequence KASRWRGRQNREKRFTF (amino acids 356-372) at the C-terminal end of its third intracellular loop. This sequence satisfies the structural criteria for G protein-activating sequences [(1992) J. Biol. Chem. 267, 8342-8346] except that the C-terminal sequence is B-B-X-X-Phe instead of B-B-X-B or B-B-X-X-B (B: basic residue, X: non-basic residue). Nevertheless, the synthetic peptide corresponding to this sequence (peptide α2-F) was found to activate Gi and Go strongly with a saturated effect at 1-3 μM. Furthermore, the substitution of the C-terminal Phe of peptide α2-F with Arg, Trp, and Tyr (but not Ala or Asp) did not appreciably affect the Gi-activating potency. It is suggested that the C-terminal basic residue of the B-B-X-X-B motif in Gi-activating sequences can be replaced by an aromatic residue.
AB - The human α2-adrenergic receptor contains the sequence KASRWRGRQNREKRFTF (amino acids 356-372) at the C-terminal end of its third intracellular loop. This sequence satisfies the structural criteria for G protein-activating sequences [(1992) J. Biol. Chem. 267, 8342-8346] except that the C-terminal sequence is B-B-X-X-Phe instead of B-B-X-B or B-B-X-X-B (B: basic residue, X: non-basic residue). Nevertheless, the synthetic peptide corresponding to this sequence (peptide α2-F) was found to activate Gi and Go strongly with a saturated effect at 1-3 μM. Furthermore, the substitution of the C-terminal Phe of peptide α2-F with Arg, Trp, and Tyr (but not Ala or Asp) did not appreciably affect the Gi-activating potency. It is suggested that the C-terminal basic residue of the B-B-X-X-B motif in Gi-activating sequences can be replaced by an aromatic residue.
KW - Aromatic amino acid
KW - G protein-activator sequence motif
KW - G-activator sequence
KW - G-coupling mechanism
KW - α-Adrenergic receptor
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U2 - 10.1016/0014-5793(92)81359-T
DO - 10.1016/0014-5793(92)81359-T
M3 - Article
C2 - 1327875
AN - SCOPUS:0026658002
SN - 0014-5793
VL - 311
SP - 29
EP - 32
JO - FEBS Letters
JF - FEBS Letters
IS - 1
ER -