Figure 4.

Feedback loops after rapalog exposure. After rapamycin, various feedback loops are triggered by ribosomal protein S6 kinase beta-1 (S6K1). The S6K1/insulin-like growth factor 1 receptor (IGF-1R)/phosphatidylinositol-3-kinase (PI3K) loop results in protein kinase B (AKT) activation, while the second loop is S6K1/IGF-IR/PI3K and mitogen-activated protein kinase (MAPK) pathway-dependent. Both loops are implicated in secondary resistance to mammalian target of rapamycin (mTOR) inhibitors. mTORC, mTOR complex; P, phosphorylated; Ras, rat sarcoma virus; TK, tyrosine kinase.