Insights into ligand pharmacology using receptor-G-protein fusion proteins

Trends in Pharmacological Sciences

Volumn 21, Issue 1, 2000, Pages 24-28

  Milligan, Graeme ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

3 ISOPROPYLAMINO 1 (7 METHYL 4 INDANYLOXY) 2 BUTANOL; ALPHA 2A ADRENERGIC RECEPTOR; BRIMONIDINE; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; GUANOSINE 5' O (3 THIOTRIPHOSPHATE); GUANOSINE TRIPHOSPHATASE; HYBRID PROTEIN; LIGAND; PERTUSSIS TOXIN;

AGONIST; DRUG PROTEIN BINDING; ENZYME KINETICS; HUMAN; HYDROPHOBICITY; LIGAND BINDING; NONHUMAN; POINT MUTATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; STOICHIOMETRY;

ANIMALS; GTP-BINDING PROTEINS; HUMANS; LIGANDS; RECEPTORS, DRUG; RECOMBINANT FUSION PROTEINS;

EID: 0033956330     PISSN: 01656147     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0165-6147(99)01404-2     Document Type: Review

References (34)

1. Bertin B.et al. Cellular signaling by an agonist-activated receptor/Gsα fusion protein. Proc. Natl. Acad. Sci. U. S. A. 91:1994;8827-8831.
2. Bertin B.et al. Activation of a β2-adrenergic receptor/Gsα fusion protein elicits a desensitization-resistant cAMP signal capable of inhibiting proliferation of two cancer cell lines. Recept. Channels. 5:1997;41-51.
3. Seifert R.et al. Different effects of Gsα splice variants on β2-adrenoreceptor-mediated signaling. The β2-adrenoreceptor coupled to the long splice variant of Gsα has properties of a constitutively active receptor. J. Biol. Chem. 273:1998;5109-5116.
4. Wenzel-Seifert K.et al. Restricting mobility of Gsα relative to the β2-adrenoceptor enhances adenylate cyclase activity by reducing Gsα GTPase activity. Biochem. J. 334:1998;519-524.
5. Seifert R.et al. Examining the efficiency of receptor/G-protein coupling with a cleavable β2-adrenoceptor-Gsα fusion protein. Eur. J. Biochem. 260:1999;661-666.
6. Loisel T.M.et al. Activation of the β2-adrenoceptor-Gsα complex leads to rapid depalmitoylation and inhibition of repalmitoylation of both the receptor and Gsα J. Biol. Chem. 274:1999;31014-31019.
7. i1α fusion protein. Biochem. J. 325:1997;17-21.
8. i1α by expressing the proteins from chimeric open reading frames. J. Biol. Chem. 272:1997;24673-24678.
9. Burt A.et al. Agonist occupation of an α2A-adrenoreceptor-Gi1α fusion protein results in activation of both receptor-linked and endogenous Gi proteins. Comparisons of their contributions to GTPase activity and signal transduction and analysis of receptor-G protein activation stoichiometry. J. Biol. Chem. 273:1998;10367-10375.
10. Carr I.C.et al. Quantitative analysis of a cysteine351glycine mutation in the G protein Gi1α: effect on α2A-adrenoceptor-Gi1α fusion protein activation. FEBS Lett. 428:1998;17-22.
11. Wise A.et al. Measurement of agonist efficacy using an α2A-adrenoceptor-Gi1α fusion protein. FEBS Lett. 419:1997;141-146.
12. Wise A.et al. Comparative analysis of the efficacy of A1 adenosine receptor activation of Gi/oα G proteins following coexpression of receptor and G protein and expression of A1 adenosine receptor-Gi/oα fusion proteins. Biochemistry. 38:1999;2272-2278.
13. i1α Mol. Pharmacol. 56:1999;684-692.
14. Medici R.et al. Efficient signal transduction by a chimeric yeast-mammalian G protein α subunit Gpa1-Gsα covalently fused to the yeast receptor ste2. EMBO J. 16:1997;7241-7249.
15. Fong C.W., Milligan G. Analysis of agonist function at fusion proteins between the IP prostanoid receptor and cognate, unnatural and chimaeric G-proteins. Biochem. J. 342:1999;457-463.
16. 351 in the rat Gαo protein. Neuropharmacology. 38:1999;1035-1041.
17. i1α Mol. Pharmacol. 55:1999;195-201.
18. 1-adenosine receptor and G protein α-subunits. J. Biol. Chem. 274:1999;30571-30579.
19. Colquhoun D. Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Br. J. Pharmacol. 125:1998;924-947.
20. Seifert R.et al. GPCR-Gα fusion proteins: molecular analysis of receptor-G-protein coupling. Trends Pharmacol. Sci. 20:1999;383-389.
21. MacEwan D.J.et al. Analysis of the role of receptor number in defining the intrinsic activity and potency of partial agonists in neuroblastoma × glioma hybrid, NG108-15, cells transfected to express differing levels of the human β2-adrenoceptor. Mol. Pharmacol. 48:1995;316-325.
22. Newman-Tancredi A.et al. Agonist and inverse agonist efficacy at human recombinant serotonin 5-HT1A receptors as a function of receptor: G-protein stoichiometry. Neuropharmacology. 36:1997;451-459.
23. 35S]guanosine-5′-O-(3-thio)triphosphate binding. Mol. Pharmacol. 54:1998;249-257.
24. Bourne H. How receptors talk to trimeric G proteins. Curr. Opin. Cell Biol. 9:1997;134-142.
25. Milligan G., Rees S. Chimaeric G α proteins: their potential use in drug discovery. Trends Pharmacol. Sci. 20:1999;118-124.
26. 35S]GTPγS binding. Biochem. Pharmacol. 55:1998;1035-1043.
27. 351 of the G protein Gi1α determines the extent of activation by the α 2A-adrenoceptor. Biochemistry. 37:1998;11555-11562.
28. Liu J.et al. Identification of a receptor/G-protein contact site critical for signaling specificity and G-protein activation. Proc. Natl. Acad. Sci. U. S. A. 92:1995;11642-11646.
29. 2-adrenergic receptor- extending the ternary complex model. J. Biol. Chem. 268:1993;4625-4636.
30. 2-adrenoceptor and type II adenylyl cyclase. Br. J. Pharmacol. 123:1998;335-343.
31. Barr A.J., Manning D.R. Agonist-independent activation of Gz by the 5-hydroxytryptamine 1A receptor co-expressed in Spodoptera frugiperda cells. Distinguishing inverse agonists from neutral antagonists. J. Biol. Chem. 272:1997;32979-32987.
32. 1A receptors by the inverse agonist, spiperone but not the neutral antagonist, WAY100,635. Br. J. Pharmacol. 120:1997;737-739.
33. Freissmuth M.et al. G protein antagonists. Trends Pharmacol. Sci. 20:1999;237-245.
34. Helper J.R. Emerging roles for RGS proteins in cell signalling. Trends Pharmacol. Sci. 20:1999;376-382.