The activation of G proteins is regulated by GEFs and GTPase activity.

<p><b>A</b> G proteins are controlled by GEFs which catalyse the sequential release and binding of guanine nucleotides, and by GTPase activity (both intrinsic and GAP-mediated) which hydrolyses bound GTP to form GDP and Pi. The red circle highlights that the GEF mechanism is completely reversible. <b>B</b> The reversible mechanism by which a GEF catalyses guanine nucleotide exchange on a G protein proceeds through a series of GEF·G protein complexes [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0151861#pone.0151861.ref013" target="_blank">13</a>]. Parameters <i>k</i>_<i>i</i> are kinetic rates which are unique to each G protein:GEF system. Associated species (free GEF, GTP, GDP) have not been drawn. The thick black arrow identifies forwards nucleotide exchange, catalysing the activation of the G protein. The thick red arrow identifies reverse nucleotide exchange, catalysing the inactivation of the G protein.