In the present study, we proposed a simplified model for positive regulation of Rho GTPases by GDIs. However, the model does not take into account GTPase cycling between membrane and cytosol. Cells contain membranous and cytoplasmic compartments, and typically, Rho GTPases function within the membranous compartments. It has been shown that the efficient cycling between inactive and active states of GTPases can occur entirely within protein complexes assembled on membrane surfaces [22]. RhoGDIs mediate the membrane-cytoplasmic shuttling of GTPases, and likely can alter the concentrations of GTPases and their RhoGDI-associated regulators at target sites in cells. Therefore, it is necessary to take into account the shuttling processes in developing a truly comprehensive model. Membrane-cytoplasmic shuttling has been considered in a simulation of the distribution of activated Cdc42 during the early phase of yeast bud formation [23]. Additionally, a modeling framework describing Rac cycling between membrane and cytosol has been reported [21]. Because our model for the Rho GTPase switch can be regarded as a basal signaling module, these studies that have taken into account the Rho GTPase shuttling processes should be incorporated into our model of the Rho GTPase switch for a more detailed and biologically-relevant model.