| Autor: |
Jackson VN; Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom., Bahia DS, Milligan G |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular pharmacology [Mol Pharmacol] 1999 Feb; Vol. 55 (2), pp. 195-201. |
| DOI: |
10.1124/mol.55.2.195 |
| Abstrakt: |
Compared with epinephrine, the relative intrinsic activity of a series of partial agonists to activate fusion proteins between the porcine alpha-2A adrenoceptor and the alpha-subunit of Gi1 was reduced after a single-point mutation (Cys351Gly) in the G protein. Although UK14304 was close to a full agonist at the fusion construct containing wild-type (Cys351)Gi1alpha, it was a partial agonist at that containing Gly351Gi1alpha. Moreover, although clonidine functioned as a good partial agonist to activate the fusion protein containing Cys351Gi1alpha, it was essentially an antagonist at the Gly351Gi1alpha-containing fusion protein. By contrast, incorporation of Ile351Gi1alpha into the fusion protein resulted in all partial agonists displaying higher intrinsic activity relative to epinephrine to activate this fusion protein than the one containing the wild-type G protein sequence. This is the first demonstration that the relative intrinsic activity of a series of agonists can be modified by a point mutation in a G protein rather than a receptor and indicates that the nature of a key contact site between a G protein and a receptor can selectively regulate partial agonist function. We provide a model for this based on the hydrophobicity of a key receptor-G protein alpha-subunit interaction interface. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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