RHEB and tuberous sclerosis: PI3K and Akt stimulation by growth factors such as IGF1 is an evolutionarily conserved function that promotes cell growth through the Akt-mediated activation of mTORC1 and the subsequent phosphorylation and inhibition of TSC2 (also known as tuberin).82 TSC1 and TSC2 are encoded by tumor suppressor genes that are mutated in tuberous sclerosis (TSC).101 The complex comprising TSC1 and TSC2 suppresses mTORC1 activity; through a C-terminal domain and a GTPase-activating protein domain, TSC2 converts Ras-related Rheb-GTP, a potent activator of mTORC1, to Rheb-GDP,102 thereby inactivating mTORC1.