Faculty Opinions recommendation of Regulated localization is sufficient for hormonal control of regulator of G protein signaling homology Rho guanine nucleotide exchange factors (RH-RhoGEFs).

Author(s):  
Andrew Goryachev
2015 ◽  
Author(s):  
Rob J Stanley ◽  
Geraint MH Thomas

G proteins are an important family of signalling molecules controlled by guanine nucleotide exchange and GTPase activity in what is commonly called an 'activation/inactivation cycle'. The molecular mechanism by which guanine nucleotide exchange factors (GEFs) catalyse the activation of monomeric G proteins is well-established, however the complete reversibility of this mechanism is often overlooked. Here, we use a theoretical approach to prove that GEFs are unable to positively control G protein systems at steady-state in the absence of GTPase activity. Instead, positive regulation of G proteins must be seen as a product of the competition between guanine nucleotide exchange and GTPase activity -- emphasising a central role for GTPase activity beyond merely signal termination. We conclude that a more accurate description of the regulation of G proteins via these processes is as a 'balance/imbalance' mechanism. This result has implications for the understanding of many intracellular signalling processes, and for experimental strategies that rely on modulating G protein systems.


2012 ◽  
Vol 288 (5) ◽  
pp. 3003-3015 ◽  
Author(s):  
Sukru Sadik Oner ◽  
Ellen M. Maher ◽  
Meital Gabay ◽  
Gregory G. Tall ◽  
Joe B. Blumer ◽  
...  

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