Reactome | AKT phosphorylates TSC2, inhibiting it

AKT phosphorylates TSC2, inhibiting it

Stable Identifier

R-HSA-198609

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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AKT phosphorylates and inhibits TSC2 (tuberin), a suppressor of the TOR kinase pathway, which senses nutrient levels in the environment. TSC2 forms a protein complex with TSC1 and this complex acts as a GAP (GTPase activating protein) for the RHEB G-protein. RHEB, in turn, activates the TOR kinase. Thus, an active AKT1 activates the TOR kinase, both of which are positive signals for cell growth (an increase in cell mass) and division.
The TOR kinase regulates two major processes: translation of selected mRNAs in the cell and autophagy. In the presence of high nutrient levels TOR is active and phosphorylates the 4EBP protein releasing the eukaryotic initiation factor 4E (eIF4E), which is essential for cap-dependent initiation of translation and promoting growth of the cell (PMID: 15314020). TOR also phosphorylates the S6 kinase, which is implicated in ribosome biogenesis as well as in the modification of the S6 ribosomal protein. AKT can also activate mTOR by another mechanism, involving phosphorylation of PRAS40, an inhibitor of mTOR activity.

Literature References

PubMed ID	Title	Journal	Year
12172553	TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling Inoki, K, Li, Y, Zhu, T, Wu, J, Guan, KL	Nat Cell Biol	2002
12150915	Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway Manning, BD, Tee, AR, Logsdon, MN, Blenis, J, Cantley, LC	Mol Cell	2002