PMID: 9419379Feb 21, 1998Paper

Controlling signaling with a specifically designed Gi-coupled receptor

Proceedings of the National Academy of Sciences of the United States of America
P CowardBruce R Conklin

Abstract

We are developing a system to control G protein signaling in vivo to regulate a broad range of physiologic responses. Our system utilizes G protein-coupled peptide receptors engineered to respond exclusively to synthetic small molecule ligands and not to their natural ligand(s). These engineered receptors are designated RASSLs (receptor activated solely by a synthetic ligand). We have made two prototype RASSLs that are based on the human kappa opioid receptor. Small molecule drugs that activate the kappa receptor are nonaddictive and safe to administer in vivo. Binding and signaling assays reveal 200-2000-fold reductions in the ability of our RASSLs to bind or be activated by dynorphin, an endogenous peptide ligand of the kappa opioid receptor. In a high-throughput signaling assay, these prototype RASSLs expressed in Chinese hamster ovary K1 cells showed little or no response to a panel of 21 opioid peptides but still signaled normally in response to small molecule drugs such as spiradoline. Activation of a RASSL by spiradoline also caused proliferation of rat-1a tissue culture cells. These data provide evidence that G protein-coupled receptors can be made into RASSLs. The potential in vivo applications for RASSLs include the p...Continue Reading

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M Gossen, H Bujard
Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·A M PaceH R Bourne
Feb 1, 1990·Trends in Pharmacological Sciences·M J Millan
Apr 1, 1989·British Journal of Pharmacology·J S ShawB G Main
Oct 1, 1995·Physiological Reviews·K Wickman, D E Clapham
Nov 12, 1993·Science·D M SpencerG R Crabtree
Aug 1, 1994·Current Opinion in Biotechnology·T W Schwartz
Jan 1, 1994·Methods in Enzymology·Y H Wong
Jan 1, 1995·Life Sciences·J ZhuL Y Liu-Chen
Jan 1, 1994·Annual Review of Biochemistry·C D StraderR A Dixon
Apr 1, 1994·Current Opinion in Cell Biology·J M Baldwin
Aug 16, 1994·Proceedings of the National Academy of Sciences of the United States of America·H KongT Reisine
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·K YasudaG I Bell
Jan 1, 1993·Progress in Drug Research. Fortschritte Der Arzneimittelforschung. Progrès Des Recherches Pharmaceutiques·R M Freidinger
Dec 1, 1996·Endocrine Reviews·T van BiesenR J Lefkowitz
May 1, 1996·Trends in Genetics : TIG·D M Spencer
Mar 1, 1997·Nature Biotechnology·Y WangB W O'Malley
Apr 1, 1997·Current Opinion in Cell Biology·H R Bourne
Apr 1, 1997·Current Opinion in Cell Biology·L Y Jan, Y N Jan

❮ Previous
Next ❯

Citations

Oct 16, 2003·Trends in Pharmacological Sciences·Petrus J Pauwels
Mar 10, 2001·European Journal of Pharmacology·F SimoninB L Kieffer
May 12, 2001·Il Farmaco·G RonsisvalleF Vittorio
Mar 10, 2001·Trends in Pharmacological Sciences·A D HowardA A Patchett
Aug 2, 2001·Trends in Pharmacological Sciences·K Scearce-LevieB R Conklin
Apr 22, 1999·Trends in Pharmacological Sciences·G Milligan, S Rees
Aug 26, 1998·Drug and Alcohol Dependence·H AkilS Watson
Jan 16, 1999·Current Opinion in Biotechnology·J E González, P A Negulescu
Jan 28, 2003·Drug Discovery Today·Kevan Shokat, Mark Velleca
Jul 27, 2001·Current Opinion in Chemical Biology·P J AlaimoK M Shokat
Aug 17, 2012·ACS Chemical Neuroscience·Mikhail G ShapiroHenry A Lester
Jan 20, 2010·ACS Chemical Neuroscience·Nuska TschammerPeter Gmeiner
Apr 28, 2006·Journal of Medicinal Chemistry·Zhan-Guo GaoKenneth A Jacobson
Mar 11, 2005·Nature·Ken L MuellerNicholas J P Ryba
Aug 1, 2008·Nature Methods·Bruce R ConklinBryan L Roth
May 21, 2010·Nature Reviews. Molecular Cell Biology·Wendell A Lim
Jan 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Edward C HsiaoRobert A Nissenson
Jul 21, 2010·The Journal of Biological Chemistry·Eugene OhStefan Herlitze
Oct 30, 2007·Journal of Toxicology and Environmental Health. Part a·William L CasleyXuguang Li
Mar 19, 2011·Pharmacological Reviews·Sarah C Rogan, Bryan L Roth
Nov 1, 2001·Annual Review of Cell and Developmental Biology·M A Shogren-KnaakK M Shokat
Oct 30, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Diana T McCloskeyAnthony J Baker
Nov 12, 2010·American Journal of Physiology. Renal Physiology·R Lance Miller
Dec 16, 2005·The AAPS Journal·Irina D PogozhevaHenry I Mosberg
Oct 29, 2013·Annual Review of Pharmacology and Toxicology·Boon Chin HengMartin Fussenegger
Aug 30, 2000·Proceedings of the National Academy of Sciences of the United States of America·S M NielsenW W Vale

❮ Previous
Next ❯

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