Figure 2.

TORC1 regulation by two classes of GTPases. In mammals, the active form of the RAG heterodimer (RAGA/B^GTP-RAGC/D^GDP) mediates mTORC1 activation by recruiting mTORC1 to lysosomes, where RHEB directly stimulates mTORC1 kinase activity. RHEB is negatively regulated by the TSC complex through its GAP activity. In budding yeast, the Gtr1^GTP-Gtr2^GDP heterodimer also promotes ScTORC1 activation. On the other hand, Rhb1, a RHEB ortholog, is not involved in ScTORC1 regulation, and TSC orthologs are absent in the budding yeast genome. Like mammalian RHEB, fission yeast Rhb1, which is negatively by the Tsc1-Tsc2 complex, is an essential activator of SpTORC1, whereas the Gtr heterodimer with GDP-bound Gtr1 plays a role in attenuating SpTORC1 activity. The guanine-nucleotide binding state of fission yeast Gtr2 does not appear to be important for SpTORC1 regulation.