“…It contains five G boxes that are involved in the recognition and hydrolysis of GTP (Urano et al, 2000). Biochemical and cell biological evidence suggests that Rheb has a low intrinsic GTPase activity and occurs preferentially in an activated, GTPbound state (Clark et al, 1997;Im et al, 2002). The tuberous sclerosis complex (TSC), a tumor suppressor formed by the TSC1 (hamartin) and TSC2 (tuberin) proteins, functions as a GTPase-activating protein (GAP) and hence as a negative regulator of Rheb (Castro et al, 2003;Garami et al, 2003;Inoki et al, 2003;Tee et al, 2003;Zhang et al, 2003).…”