Loss of activation of Gs but not Gi following expression of an α2A‐adrenoceptor‐Gi1α fusion protein

FEBS Letters

Milligan, Graeme¹  Sautel, Martine¹ 

[1] Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, UK

关键词: Receptor;    G protein;    Adrenaline;    Adenylyl cyclase;    GPCR;    G protein-coupled receptor;    G protein;    guanine nucleotide binding protein;    AC;    adenylyl cyclase;   

DOI  :  10.1016/S0014-5793(98)01094-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Both the porcine α_2A-adrenoceptor and a fusion protein between this receptor and a pertussis toxin-resistant form of G_i1α were stably expressed in Rat-1 fibroblasts. The agonist UK14304 mediated a biphasic regulation of adenylyl cyclase activity via the isolated receptor with inhibition of the enzyme activity at low concentrations of the compound which was subsequently reversed at higher concentrations. By contrast, stimulation of the fusion protein with this agonist could only produce inhibition of enzyme activity. This inhibition was produced by activation of endogenous G_i rather than the fused α subunit of G_i1, as pertussis toxin treatment obliterated inhibitory regulation of adenylyl cyclase via the fusion construct. Pertussis toxin treatment potentiated stimulation of adenylyl cyclase via the isolated receptor but such treatment was unable to uncover capacity of the fusion protein to produce such an effect.

【 授权许可】

Unknown