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. 2016 Aug;6(4):339–347. doi: 10.1212/CPJ.0000000000000260

Figure 1. Mechanistic target of rapamycin (mTOR) pathway.

Figure 1

There are many components of the upstream and downstream pathways of the regulation of mTOR. Under normal physiologic conditions, some of the upstream pathways are activated by hypoxia and cellular stress. Serine/threonine kinase 11 (STK11) (also known as LKB1) is induced by hypoxia and cellular stress, which is further activated by adenosine monophosphate (AMP) and induces adenosine monophosphate-activated protein kinase (AMPK), which further activates the TSC1/TSC2 complex, which inhibits Ras homolog enriched in brain (Rheb) and therefore downregulates mTOR. Hypoxia-inducible factor 1-α (HIF1-α) is induced by hypoxia, which in turn activates regulated in development and DNA damage responses 1 (REDD1), which induces TSC1/TSC2. There are multiple growth factors and cytokines, which induce protein kinase B, also known as Akt (PKB), extracellular signal-regulated kinase (ERK), ribosomal protein S6 kinase (RSK), and inhibitor of nuclear factor κ-B kinase subunit β (IKKβ), and all inhibit the TSC1 and TSC2 complex, as seen in the diagram. The activation of mTOR leads to cell growth.