RT Journal Article
SR Electronic
T1 Activation of G proteins by guanine nucleotide exchange factors relies on GTPase activity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 032607
DO 10.1101/032607
A1 Stanley, Rob J
A1 Thomas, Geraint MH
YR 2015
UL http://biorxiv.org/content/early/2015/11/23/032607.abstract
AB 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.