Conclusions
We constructed models of the Rho GTPase cycle in which RhoGDIs inhibit the activities of GEFs and GAPs by physically interacting with them, as well as by sequestering the Rho GTPases. This model showed that the functions of GEFs and GAPs are integrated into Rho GTPase signaling through the interactions of these regulators with GDIs, and thus, the interconversion between transient and sustained Rho activation occurs by changes mainly in the affinities of GDIs to GAPs and the concentrations of GAPs. These results provide new insights into the physiological roles of Rho GTPase signaling.