Coordinate regulation of G protein signaling via dynamic interactions of receptor and GAP.

PLoS Computational Biology
Marc TurcotteElliott M Ross

Abstract

Signal output from receptor-G-protein-effector modules is a dynamic function of the nucleotide exchange activity of the receptor, the GTPase-accelerating activity of GTPase-activating proteins (GAPs), and their interactions. GAPs may inhibit steady-state signaling but may also accelerate deactivation upon removal of stimulus without significantly inhibiting output when the receptor is active. Further, some effectors (e.g., phospholipase C-beta) are themselves GAPs, and it is unclear how such effectors can be stimulated by G proteins at the same time as they accelerate G protein deactivation. The multiple combinations of protein-protein associations and interacting regulatory effects that allow such complex behaviors in this system do not permit the usual simplifying assumptions of traditional enzyme kinetics and are uniquely subject to systems-level analysis. We developed a kinetic model for G protein signaling that permits analysis of both interactive and independent G protein binding and regulation by receptor and GAP. We evaluated parameters of the model (all forward and reverse rate constants) by global least-squares fitting to a diverse set of steady-state GTPase measurements in an m1 muscarinic receptor-G(q)-phospholipase...Continue Reading

References

Jan 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·L E Limbird, R J Lefkowitz
Sep 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·D Cassel, Z Selinger
Jan 1, 1991·Annual Review of Biochemistry·Y KaziroT Satoh
Sep 1, 1994·Biophysical Journal·P A Mahama, J J Linderman
Nov 9, 1994·Molecular and Cellular Biochemistry·T W Traut
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T KozasaA G Gilman
Jan 1, 1996·Annual Review of Pharmacology and Toxicology·T GudermannG Schultz
Aug 21, 1996·Journal of Theoretical Biology·J M WeissT P Kenakin
Nov 1, 1996·Journal of Pharmacological and Toxicological Methods·M W LutzT Rimele
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·D E Clapham, E J Neer
Jan 1, 1997·Annual Review of Biochemistry·S R Sprang
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·C A DoupnikP Kofuji
May 4, 1999·Trends in Cell Biology·L De Vries, M Gist Farquhar
Jul 14, 1999·Biochemical Pharmacology·P ChidiacE M Ross
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·S Mukhopadhyay, E M Ross
Oct 19, 2002·Circulation Research·Randy A Hall, Robert J Lefkowitz
Dec 4, 2002·Nature Reviews. Molecular Cell Biology·Jin ZhangRoger Y Tsien
Jan 14, 2003·Biophysical Journal·Peter J Woolf, Jennifer J Linderman
Jan 25, 2003·European Journal of Biochemistry·Hong QianShou-dan Liang
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Tau-Mu YiMelvin I Simon
Oct 4, 2003·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Kevin S Brown, James P Sethna
Dec 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Moritz BünemannMartin J Lohse
Jun 23, 2004·Journal of Theoretical Biology·Peter J Woolf, Jennifer J Linderman
Aug 10, 2004·Yeast·Bente Kofahl, Edda Klipp
Nov 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Scott J BornheimerShankar Subramaniam
May 4, 2005·The Journal of Biological Chemistry·Monika FrankMoritz Bünemann
Jan 13, 2006·Annual Review of Pharmacology and Toxicology·Motohiko SatoStephen M Lanier
Jan 13, 2006·Nature Chemical Biology·Jean-Pierre VilardagaMartin J Lohse
Sep 23, 2006·The Biochemical Journal·Vladimir L Katanaev, Matey Chornomorets

❮ Previous
Next ❯

Citations

Nov 13, 2012·Annual Review of Physiology·Ganesh Kadamur, Elliott M Ross
Jan 27, 2010·The Journal of General Physiology·Björn H FalkenburgerBertil Hille
Mar 31, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nevin A LambertDavid P Siderovski
Oct 13, 2011·Chemical Reviews·T Kendall HardenJohn Sondek
Oct 13, 2009·Biochemical and Biophysical Research Communications·Irene Litosch
Mar 17, 2009·Cellular Signalling·Benjamin SmithGraham Ladds
Apr 18, 2014·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Patrick R O'NeillN Gautam
Mar 26, 2016·Life Sciences·Irene Litosch
Sep 15, 2010·Journal of Receptor and Signal Transduction Research·Jean-Pierre Vilardaga
Nov 17, 2012·Plant Signaling & Behavior·Nguyen PhanAlan M Jones
Feb 10, 2011·Science Signaling·Elliott M Ross
Dec 31, 2016·Molecular Systems Biology·Alan BushAlejandro Colman-Lerner
Jul 15, 2015·Molecular Pharmacology·S RothF J Bruggeman
Aug 27, 2017·The Journal of Biological Chemistry·Punya NavaratnarajahElliott M Ross
Sep 24, 2020·Progress in Lipid Research·Matilda Katan, Shamshad Cockcroft
Sep 13, 2008·Current Biology : CB·Elliott M Ross
Oct 29, 2011·Biochemical and Biophysical Research Communications·Irene Litosch

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
nucleotide exchange
fluorescence

Software Mentioned

SNT
Mathematica
Matlab
ode15s

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.