Figure 1.

Rapamycin-sensitive signal transduction pathways. Both rapamycin and rapamycin analogs bind to the immunophilin FK506 binding protein-12 (FKBP-12). The rapamycin-FKBP12 complex binds to mammalian target of rapamycin (mTOR), inhibiting its kinase activity, which in turn inhibits the phosphorylation and activation of the downstream translational regulators 4EBP1/PHAS-1 and p70^S6K. These downstream effects decrease the translational processing of mRNA for specific proteins that are essential for G₁ to S phase transition. 4E-BP1, 4E binding protein-1; GF, growth factor; GPB, growth factor receptor bound; MAP, mitogen activated protein kinase; PI3K, phosphatidylinositol 3-kinase; PHAS, phosphorylated heat and acid stable protein; pRb, retinoblastoma protein; PTEN, phosphatase and tensin homologue deleted from chromosome 10; RAP, rapamycin; SOS, son-of-sevenless; TSC, tuberous sclerosis complex.