Abstract
Gz couples to most of the known Gi-linked receptors and its α subunit (Gαz) inhibits adenylyl cyclases as efficiently as Gαi subtypes. A series of chimeric Gα subunits with different portions of Gαz and Gαt1 (a regulator of cGMP phosphodiesterase) were constructed to study the essential structural elements of Gαz that determine receptor coupling and effector interaction. The receptor-mediated functions of the chimeras were assessed in two aspects: 1) stimulation of type 2 adenylyl cyclase through the release of βγ subunits from the chimeras, and 2) inhibition of isoproterenol-stimulated adenylyl cyclase by the chimeric Gα subunits. The results suggested that the presence of both termini of Gαz were critical for coupling to δ-opioid receptor, with the N-terminal region being more important. Moreover, a stretch of amino acids (295–319) corresponding to the α4/β6 loop was identified as one of the adenylyl cyclase inhibitory domains of Gαz.
Footnotes
- Received April 3, 2000.
- Accepted July 24, 2000.
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Send reprint requests to: Dr. Yung H. Wong, Department of Biochemistry and Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. E-mail: boyung{at}ust.hk
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This work was supported in part by the Hong Kong Jockey Club and Grants HKUST 567/95M and 6096/98M from the Research Grants Council of Hong Kong to Y.H.W.
- The American Society for Pharmacology and Experimental Therapeutics
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