p-AMPK phosphorylates TSC1:TSC2

Stable Identifier
R-HSA-380927
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Activated AMPK (phosphorylated on the alpha subunit and with AMP bound) phosphorylates TSC2 (also known as tuberin) on Ser-1387, thereby activating the GTPase activating protein (GAP) activity of the Tuberous Sclerosis Complex (TSC). The TSC tumor suppressor is a critical upstream inhibitor of the mTORC1 complex. TSC is a GTPase-activating protein that stimulates the intrinsic GTPase activity of the small G-protein Rheb. This inactivates Rheb by stimulating its GTPase activity. The GDP-bound form of Rheb looses the ability to activate the kinase activity of the mTORC1 complex (Sancak et al. 2007). Loss of TSC1 or TSC2 leads to hyperactivation of mTORC1.

Phosphorylation of TSC1 and TSC2 serves as an integration point for a wide variety of environmental signals that regulate mTORC1 (Sabatini 2006). Mitogen-activated kinases including Akt, Erk, and Rsk directly phosphorylate TSC2, leading to its inactivation by an unknown mechanism. Another Akt substrate, PRAS40, was recently shown to bind and inhibit the mTORC1 complex. Upon phosphorylation by Akt, PRAS40 no longer inhibits mTORC1 (Sancak et al. 2007; Vander Haar et al. 2007).

Literature References
PubMed ID Title Journal Year
14651849 TSC2 mediates cellular energy response to control cell growth and survival

Inoki, K, Zhu, T, Guan, KL

Cell 2003
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
AMP-activated protein kinase activity of p-AMPK heterotrimer:AMP [cytosol]
Physical Entity
Activity
Orthologous Events
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Created