Reactome | Energy dependent regulation of mTOR by LKB1-AMPK

Energy dependent regulation of mTOR by LKB1-AMPK

Stable Identifier

R-HSA-380972

DOI

10.3180/REACT_21387.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Energy dependent regulation of mTOR by LKB1-AMPK

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Upon formation of a trimeric LKB1:STRAD:MO25 complex, LKB1 phosphorylates and activates AMPK. This phosphorylation is immediately removed in basal conditions by PP2C, but if the cellular AMP:ATP ratio rises, this activation is maintained, as AMP binding by AMPK inhibits the dephosphorylation. AMPK then activates the TSC complex by phosphorylating TSC2. Active TSC activates the intrinsic GTPase activity of Rheb, resulting in GDP-loaded Rheb and inhibition of mTOR pathway.

Literature References

PubMed ID	Title	Journal	Year
17712357	AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy Hardie, DG	Nat Rev Mol Cell Biol	2007
17010524	The LKB1 tumor suppressor kinase in human disease Katajisto, P, Vallenius, T, Vaahtomeri, K, Ekman, N, Udd, L, Tiainen, M, Mäkelä, TP	Biochim Biophys Acta	2007
17613433	Defining the role of mTOR in cancer Guertin, DA, Sabatini, DM	Cancer Cell	2007