Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Dual positive and negative regulation of GPCR signaling by GTP hydrolysis

Tools
- Tools
+ Tools

Smith, Benjamin, Hill, Claire, Godfrey, Emma L., Rand, D. A., Berg, Hugo van den, Thornton, Steven, Hodgkin, Matthew N., Davey, John and Ladds, Graham (2009) Dual positive and negative regulation of GPCR signaling by GTP hydrolysis. Cellular Signalling, Vol.21 (No.7). pp. 1151-1160. doi:10.1016/j.cellsig.2009.03.004

[img]
Preview
PDF
WRAP_Ladds_9576638_060309_Smith_et_al_2009.pdf - Requires a PDF viewer.

Download (490Kb)
Official URL: http://dx.doi.org/10.1016/j.cellsig.2009.03.004

Request Changes to record.

Abstract

G protein-coupled receptors (GPCRs) regulate a variety of intracellular pathways through their ability to promote the binding of GTP to heterotrimeric G proteins. Regulator of G protein signaling (RGS) proteins increase the intrinsic GTPase activity of G-subunits and are widely regarded as
negative regulators of G protein signaling. Using yeast we demonstrate that GTP hydrolysis is not only required for desensitization, but is essential for achieving a high maximal (saturated level) response. Thus RGS-mediated GTP hydrolysis acts as both a negative (low stimulation) and
positive (high stimulation) regulator of signaling. To account for this we generated a new kinetic model of the G protein cycle where GGTP enters an inactive GTP-bound state following effector activation. Furthermore, in vivo and in silico experimentation demonstrates that maximum signaling output first increases and then decreases with RGS concentration. This unimodal, non-monotone
dependence on RGS concentration is novel. Analysis of the kinetic model has revealed a dynamic network motif that shows precisely how inclusion of the inactive GTP-bound state for the G produces this unimodal relationship.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Faculty of Science > Molecular Organisation and Assembly in Cells (MOAC)
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): G proteins, Computer simulation
Journal or Publication Title: Cellular Signalling
Publisher: Elsevier Inc.
ISSN: 0898-6568
Official Date: July 2009
Dates:
DateEvent
July 2009Published
Volume: Vol.21
Number: No.7
Number of Pages: 10
Page Range: pp. 1151-1160
DOI: 10.1016/j.cellsig.2009.03.004
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Engineering and Physical Sciences Research Council (EPSRC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), University Hospitals Coventry and Warwickshire NHS Trust
Grant number: BB/G01227X/1 (BBSRC)

Data sourced from Thomson Reuters' Web of Knowledge

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us