Monday 12 March 2007

senescence - Do we know if RHEB is more sensitive to some amino acids than other amino acids?

RHEB does not sense amino acids. See the abstract of this paper.




Activation of this pathway requires inhibition of the tumor suppressor
complex TSC1/2. TSC2 is a GTPase-activating protein for the small
GTPase Ras homologue enriched in brain (Rheb), GTP loading of which
activates mTOR by a yet unidentified mechanism. The level at which
this pathway senses the availability of amino acids is unknown but is
suggested to be at the level of TSC2. Here, we show that amino-acid
depletion completely blocks insulin- and TPA-induced Rheb activation.
This indicates that amino-acid sensing occurs upstream of Rheb.
Despite this, amino-acid depletion can still inhibit mTOR/S6 kinase
signaling in TSC2-/- fibroblasts. Since under these conditions
Rheb-GTP levels remain high, a second level of amino-acid sensing
exists, affecting mTOR activity in a Rheb-independent fashion.




RHEB also doesn't have any amino-acid binding (or any small molecule binding) domain.

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