FIGURE 1.

Delineation of signaling pathways that mediate growth factor-stimulated mTORC1 activation. A, mTORC1 is activated via Akt phosphorylation and neutralization of negative regulators, TSC2 and PRAS40. ERK-dependent neutralization of TSC2 has also been reported. The black arrows and red bars signify positive and negative regulation, respectively. PIP₃, phosphoinositide 3,4,5-trisphosphate. B, in NIH 3T3 cells, PDGF-BB stimulation (1 nm, 15 min) elicits phosphorylation (p) of ERK, Akt, TSC2, and S6K1; the latter is blocked by rapamycin (100 nm). The MEK inhibitor U0126 (10 μm) blocks ERK activation but has no discernible effect on mTORC1-dependent S6K1 phosphorylation. Akt inhibitor VIII (Akt In-VII, 10 μm) blocks the phosphorylation of Akt and TSC2 as expected and ablates S6K1 phosphorylation. C, Akt inhibitor VIII (10 μm) also blocks phosphorylation of PRAS40 Thr²⁴⁶ as expected.