Growth factor (EGF) binding to its respective RTK (EGFR) activates PI3K, resulting in conversion of PIP2 to PIP3. In turn, PIP3 initiates a PDK1-dependent cascade that activates AKT, which in turn phosphorylates TSC, resulting in inhibition of the tonic mTORC1 inhibitor RHEB. mTORC1 is recruited into a large protein complex on the lysosome surface composed of RAG GTPase, Ragulator, V-ATPase, and the amino acid transporter SLC38A9, allowing mTORC1 to be activated via inhibition of RHEB. Constitutive activation of this pathway via deletion of PTEN, which converts PIP3 to PIP2, results in proximal tubular hypertrophy during maturation. Uninephrectomy causes an immediate increase in renal blood flow, which enhances renal amino acid content. These amino acids activate mTORC1 by a process requiring class III PI3K (VPS34), which is involved in endocytosis and vesicle recycling from the Golgi to the lysosome. Several recent studies have implicated intracellular membrane trafficking in the process by which some amino acids activate the mTORC1 pathway. mTORC1 is present in the ER and TGN, and the complex appears to traffic to the lysosome via vesicles, as its activation is blocked by loss of RAB1A, known to regulate ER-to-Golgi transport, or ARF, known to mediate budding from the Golgi. Transport to the lysosome likely occurs via a VPS34-mediated pathway. The TGN is slightly acidic (~pH = 6.4, yellow), and as vesicles move to the lysosome (~pH = 4.5–5, dark orange), they become increasingly acidic. It is not clear whether mTORC1 can be activated by amino acids when in the Golgi without prior transport to the lysosome.