Kinetics of G-protein-coupled receptor signalling and desensitization
Biochem Soc Trans, 32 (Pt 6):
1029-31 (December 2004)Krasel, C Vilardaga, J-P Bunemann, M Lohse, M J Research Support,
Non-U.S. Gov't England Biochemical Society transactions Biochem Soc
Trans. 2004 Dec;32(Pt 6):1029-31..Abstract
The kinetics of G-protein-coupled receptor activation and deactivation
has, so far, been measured only indirectly, most frequently by assessing
the production of various second messengers. We have developed methods
based on fluorescence resonance energy transfer to quantify the kinetics
of receptor activation by agonist (measured as conformational change
in the receptor), the kinetics of G-protein activation (measured
as G-protein subunit rearrangement) and the kinetics of receptor
inactivation by arrestins (measured as receptor-arrestin interaction).
Using these methods, we show that receptor activation by agonists
and signalling to G-proteins occur on the subsecond time scale, whereas
receptor desensitization is limited by receptor phosphorylation and
proceeds more slowly.