**3.1 Regulators of the Rho GTPases**

Like all members of the Ras superfamily, the activity of the Rho GTPases is tightly controlled by the ratio of their GTP/GDP-bound forms in the cell (Fig. 1)(Scheffzek and Ahmadian 2005).

Fig. 1. Regulation of Rho family proteins.

The cycle of activation/inactivation of Rho family GTPases is under the regulation of three distinct families of proteins: GEFs, guanine nucleotide exchange factors catalyze nucleotide exchange when activated by upstream signals; GAPs, GTPase-activating proteins promote the GTP hydrolisis; GDIs, guanine nucleotide dissociation inhibitors block both nucleotide hydrolisis and exchange and participate in Rho GTPase movement between cytosol and membranes.

Rho-specific guanine nucleotide exchange factors (RhoGEFs) activate Rho proteins by facilitating the exchange of GDP for GTP. Rho GTPase activating proteins (RhoGAPs) stimulate the intrinsic rate of hydrolysis of Rho proteins, thus converting them into their inactive state. While Rho-specific guanine nucleotide dissociation inhibitors (RhoGDIs) compete with RhoGEFs for binding to GDP-bound Rho proteins, and sequester Rho in the inactive state (Olofsson 1999).
