Summary of the AMPK and mTOR signaling pathways

Summary of the AMPK and mTOR signaling pathways. Phosphatidylinositol 3 kinase (PI3K) is activated when growth factors bind to their receptors. Phosphatidylinositol bisphosphate (PIP2) is converted by PI3K into phosphatidylinositol trisphosphate (PIP3). This leads to activation of phosphoinositide-dependent protein kinase-1 (PDK1). PDK1 phosphorylates Akt1 to partially activate it and prime it for further activation. Full activation is dependent on an additional phosphorylation of Akt1by mTORC2, a complex that includes the kinase, mammalian target of rapamycin (mTOR) and the regulatory subunit Rictor. Akt1 phosphorylates and activates the mTORC1 complex that contains mTOR and the regulatory subunit Raptor. mTORC1 phosphorylates the translation repressor 4EBP and inactivates it. AMPK is known to inhibit mTORC1 activation at multiple levels. More detail can be found in Refs. , . We propose that cordycepin activates AMPK by an unknown mechanism and that active AMPK somehow also inhibits mTORC2 activity (interactions shown in red), leading to a double block of the mTOR signaling pathway.

Publication

Cordycepin Inhibits Protein Synthesis and Cell Adhesion through Effects on Signal Transduction. (2010) Ying Ying Wong, et al. J Biol Chem. 2010 Jan 22;285(4):2610-2621. Figure: F8. All organisms Mus musculus Homo sapiens Bos taurus Oryctolagus cuniculus Drosophila melanogaster

Disease mentions