Figure 5. Flips between signalling modes.

The trimeric G-protein signalling system can flip from one mode to another and back upon changes in conditions. At zero time, the system is stimulated with 1 nM activated GPCR, and later with 5 nM; both stimulations result in increasing activation of the system in mode 1. Further increase in the GPCR activation (20 nM and then 90 nM) results in a switch to mode 2 of system activation. Concentration of the GAP is originally modelled at 10 nM; stepwise increases in GAP concentration lead to reduction and then loss of the Gα^GTP levels, switching the system back to mode 1; importantly, the system is still activated, and levels of βγ remain high. Kinetic parameters, other than those shown, are as in Figure 3, except for k_ass which is 0.0005 nM⁻¹·s⁻¹.