Figure 1.

A network of oncogenes and tumor suppressors regulates the mTORC1-signaling pathway. Growth factors bind and stimulate receptor tyrosine kinases (RTKs), which can activate both the PI3K-Akt and Ras-ERK signaling pathways. These upstream signals inhibit the TSC1-TSC2 complex allowing Rheb to activate mTORC1. Activated mTORC1 phosphorylates two direct substrates, the ribosomal S6 kinases (S6K1 and S6K2), and translation repressors 4E-BP1 and 4E-BP2. Cellular energy depletion results in the activation of AMP-activated protein kinase (AMPK) by the tumor suppressor protein LKB1 serine/threonine kinase. AMPK phosphorylates and enhances the GAP function of TSC2 towards Rheb. In addition, AMPK directly phosphorylates the mTORC1 component raptor. Both events result in the inhibition of mTORC1 in response to energy stress. Within this signaling network lie many oncogenes (depicted in red) and tumor suppressors (depicted in blue).

Csibi and Blenis BMC Biology 2011 9:69   doi:10.1186/1741-7007-9-69
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