The GTPase cycle. RhoGDIs (1) sequester Rho GTPases in the cytoplasm and prevent GDP dissociation until released by RhoGDFs (2). The Rho protein attaches to the inner cytoplasmic membrane by prenylation of the protein. When a protein tyrosine kinase growth factor receptor (3), such as EGFR, is activated, p120 RasGAP is phosphorylated and forms a heterodimer with p190 RhoGAP, leading to inactivation of those proteins. The RhoGEF proteins (4) are also phosphorylated, causing exchange of GDP for GTP (6) on the Rho proteins, leading to Rho activation. Active, GTP-bound Rho proteins activate downstream Rho effector proteins (7), which stimulate cellular motility and invasion (8). RhoGAP (9) is released and activated, catalyzing the hydrolysis of GTP to GDP (10) and inactivating the Rho protein. EGFR = EGF receptor; GAP = GTPase activating factor; GDF = GDI-dissociation factor; GDI = guanine nucleotide dissociation inhibitor; GDP = guanosine diphosphate ; GEF = guanine nucleotide exchange factor; GTP = guanosine triphosphate.