Energy dependent regulation of mTOR by LKB1-AMPK

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.

在LKB1:STRAD:MO25三聚体复合物形成之际，LKB1通过磷酸化激活AMPK。在基础条件下，此磷酸化作用随即被PP2C去除，然而，若细胞内AMP:ATP比例上升，此激活状态得以持续，因AMP与AMPK的结合抑制了去磷酸化过程。随后，AMPK通过磷酸化TSC2激活TSC复合物。活性化的TSC进而激活Rheb的内源GTPase活性，导致GDP结合的Rheb形成，并抑制mTOR通路。