Fig. 1. Regulation of Rho family proteins. Most Rho proteins are active when bound to GTP, and inactive when bound to GDP. They are activated in response to extracellular signals including soluble cytokines, growth factors and extracellular matrix proteins. Activation is catalysed by exchange factors (GEFs) and inactivation by GTPase-activating proteins (GAPs). Several Rho family proteins also bind to guanine-nucleotide-dissociation inhibitors (GDIs) in the cytoplasm, and are inactive in this complex. Their activation therefore also depends on dissociation of GDI. When bound to GTP, they interact with target proteins to induce downstream responses.