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.
Hardie, DG
Vaahtomeri, K, Vallenius, T, Tiainen, M, Katajisto, P, Ekman, N, Udd, L, Mäkelä, TP
Sabatini, DM, Guertin, DA
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