Rheb is a Ras-like small GTPase essential for TORC1 activity in mammals []. Rheb activates the protein kinase activity of mTORC1 (rapamycin), and in turn stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling [, , ]. Rheb alternates between an inactive form bound to GDP and an active form bound to GTP. It is inactivated by TSC1-TSC2 via the GTPase activating protein (GAP) domain of TSC2 []. The mechanism of action of Rheb has been determined from the tertiary structure [].
RagA and RagB are closely related Rag GTPases (ras-related GTP-binding protein A and B) that constitute a unique subgroup of the Ras superfamily [], and are functional homologues of Saccharomyces cerevisiaeGtr1 []. They function by forming heterodimers with RagC or RagD, and similarly, Gtr1 dimerizes with Gtr2, through the carboxy-terminal segments. They play an essential role in regulating amino acid-induced target of rapamycin complex 1 (TORC1) kinase signaling [], exocytic cargo sorting at endosomes, and epigenetic control of gene expression. In response to amino acids, the Rag GTPases guide the TORC1 complex to activate the platform containing Rheb proto-oncogene by driving the relocalization of mTORC1 from discrete locations in the cytoplasm to a late endosomal and/or lysosomal compartment that is Rheb-enriched and contains Rab-7 [].
RagC and RagD are closely related Rag GTPases (ras-related GTP-binding protein C and D) that constitute a unique subgroup of the Ras superfamily [], and are functional homologues of Saccharomyces cerevisiaeGtr2. They form heterodimers with RagA or RagB [], and similarly, Gtr2 dimerizes with Gtr1 in order to function. They play an essential role in regulating amino acid-induced target of rapamycin complex 1 (TORC1) kinase signaling [], exocytic cargo sorting at endosomes, and epigenetic control of gene expression. In response to amino acids, the Rag GTPases guide the TORC1 complex to activate the platform containing Rheb proto-oncogene by driving the relocalization of mTORC1 from discrete locations in the cytoplasm to a late endosomal and/or lysosomal compartment that is Rheb-enriched and contains Rab-7 [].
