![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 57, Issue 3, 602-609, March 2000
Laboratory for Molecular Pharmacology, Department of Pharmacology,
The Panum Institute, University of Copenhagen, DK-2200 Copenhagen,
Denmark
ORF-74, a 7TM receptor oncogene encoded by human herpes virus 8, shows 50% constitutive activity in stimulating phosphatidylinositol turnover and binds a large variety of CXC chemokines. These endogenous ligands cover a full spectrum of pharmacological properties with growth-related oncogene (GRO)-
and -
functioning as full
agonists; GRO
as a partial agonist; interleukin (IL)-8,
neutrophil-activating peptide (NAP)-2, and epithelial cell-derived
activating peptide (ENA)-78 as neutral ligands; granulocyte
colony-stimulating factor (GCP)-2 as a partial inverse agonist;
and interferon-gamma inducible protein (IP)-10 and stromal cell-derived
factor (SDF)-1 as full inverse agonists. The affinity for the
agonists was independent of whether it was determined in competition
binding against the agonist 125I-GRO, against the
inverse agonist 125I-IP-10, or against the neutral ligand
125I-IL-8. Similarly, the affinities of the inverse
agonists were within 1 order of magnitude independent of the choice of
radioligand. In contrast, the neutral ligands IL-8, NAP-2, and ENA-78,
which all displaced 125I-IL-8 with single-digit nanomolar
affinity showed up to 1000-fold lower affinity against both the
radioactive agonist and against the radioactive inverse agonist. A
close correlation was observed between the EC50 values for
the ligands and their IC50 values measured against either
radioactive agonist or radioactive inverse agonist, but a poor
correlation was found to the IC50 value measured against
the neutral ligand. It is concluded that in ORF-74, ligands compete for
binding more according to pharmacological property than to structural
homology and that both agonists and inverse agonists, in contrast to
neutral ligands, apparently bind with high affinity either to a common
conformation of the receptor or to readily interconvertible states, not
available for the neutral ligands.
This article has been cited by other articles:
|
|
 |
|
  P. C. Jensen, S. Thiele, T. Ulven, T. W. Schwartz, and M. M. Rosenkilde Positive Versus Negative Modulation of Different Endogenous Chemokines for CC-chemokine Receptor 1 by Small Molecule Agonists through Allosteric Versus Orthosteric Binding J. Biol. Chem., August 22, 2008; 283(34): 23121 - 23128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Boudry, N. Markine-Goriaynoff, C. Delforge, J.-Y. Springael, L. de Leval, P. Drion, G. Russell, D. M. Haig, A. F. Vanderplasschen, and B. Dewals The A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protein-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits J. Gen. Virol., December 1, 2007; 88(12): 3224 - 3233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Rosenkilde, R. David, I. Oerlecke, T. Benned-Jensen, U. Geumann, A. G. Beck-Sickinger, and T. W. Schwartz Conformational Constraining of Inactive and Active States of a Seven Transmembrane Receptor by Metal Ion Site Engineering in the Extracellular End of Transmembrane Segment V Mol. Pharmacol., December 1, 2006; 70(6): 1892 - 1901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Verzijl, L. Pardo, M. van Dijk, Y. K. Gruijthuijsen, A. Jongejan, H. Timmerman, J. Nicholas, M. Schwarz, P. M. Murphy, R. Leurs, et al. Helix 8 of the Viral Chemokine Receptor ORF74 Directs Chemokine Binding J. Biol. Chem., November 17, 2006; 281(46): 35327 - 35335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wen, S. F. Giardina, D. Hamming, J. Greenman, E. Zachariah, M. D. Bacolod, H. Liu, J. Shia, P. S. Amenta, F. Barany, et al. GRO{alpha} Is Highly Expressed in Adenocarcinoma of the Colon and Down-Regulates Fibulin-1. Clin. Cancer Res., October 15, 2006; 12(20): 5951 - 5959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Wu, K. Ottow, P. Poulsen, R. F. Gaber, E. Albers, and M. C. Kielland-Brandt Competitive intra- and extracellular nutrient sensing by the transporter homologue Ssy1p J. Cell Biol., May 8, 2006; 173(3): 327 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cannon, E. Cesarman, and C. Boshoff KSHV G protein-coupled receptor inhibits lytic gene transcription in primary-effusion lymphoma cells via p21-mediated inhibition of Cdk2 Blood, January 1, 2006; 107(1): 277 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Rosenkilde, K. A. McLean, P. J. Holst, and T. W. Schwartz The CXC Chemokine Receptor Encoded by Herpesvirus saimiri, ECRF3, Shows Ligand-regulated Signaling through Gi, Gq, and G12/13 Proteins but Constitutive Signaling Only through Gi and G12/13 Proteins J. Biol. Chem., July 30, 2004; 279(31): 32524 - 32533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kenakin Efficacy as a Vector: the Relative Prevalence and Paucity of Inverse Agonism Mol. Pharmacol., January 1, 2004; 65(1): 2 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Richard, S. Barroso, J. Martinez, C. Labbe-Jullie, and P. Kitabgi Agonism, Inverse Agonism, and Neutral Antagonism at the Constitutively Active Human Neurotensin Receptor 2 Mol. Pharmacol., December 1, 2001; 60(6): 1392 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. KENAKIN Inverse, protean, and ligand-selective agonism: matters of receptor conformation FASEB J, March 1, 2001; 15(3): 598 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Ho, N. Ganeshalingam, A. Rosenhouse-Dantsker, R. Osman, and M. C. Gershengorn Charged Residues at the Intracellular Boundary of Transmembrane Helices 2 and 3 Independently Affect Constitutive Activity of Kaposi's Sarcoma-associated Herpesvirus G Protein-coupled Receptor J. Biol. Chem., January 5, 2001; 276(2): 1376 - 1382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Holst, H. Hastrup, U. Raffetseder, L. Martini, and T. W. Schwartz Two Active Molecular Phenotypes of the Tachykinin NK1 Receptor Revealed by G-protein Fusions and Mutagenesis J. Biol. Chem., June 1, 2001; 276(23): 19793 - 19799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Mizoue, S. K. Sullivan, D. S. King, T. N. Kledal, T. W. Schwartz, K. B. Bacon, and T. M. Handel Molecular Determinants of Receptor Binding and Signaling by the CX3C Chemokine Fractalkine J. Biol. Chem., August 31, 2001; 276(36): 33906 - 33914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Marie, E. Richard, D. Pruneau, J.-L. Paquet, C. Siatka, R. Larguier, C. Ponce, P. Vassault, T. Groblewski, B. Maigret, et al. Control of Conformational Equilibria in the Human B2 Bradykinin Receptor. MODELING OF NONPEPTIDIC LIGAND ACTION AND COMPARISON TO THE RHODOPSIN STRUCTURE J. Biol. Chem., October 26, 2001; 276(44): 41100 - 41111. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
