How do people usually check if mTORC1 is activated? By checking if S6K1 is phosphorylated? How does mTORC1 get activated? Also by phosphorylation or is it transcriptionally regulated?
p70S6K phosphorylation is an useful read out for mTORC1 activation. As the previous post suggested, Laplante and Sabatini's review thoroughly describes the pathways leading to mTOR activation, most of which depend on TSC1/2 signaling. The TSC1/2 complex is upstream mTOR and acts as a GAP for the small GTPase Rheb, maintaining it in a GDP-bound, inactive state. When the TSC1/2 complex is inhibited, Rheb bounds GTP: Once in its active form, GTP-Rheb directly interacts with mTORC1 leading to mTORC1 activation, although the exact mechanism by which this interaction is able to activate mTORC1 complex remains unknown (as far as I'm aware of).
Dear Nicole,
we checked if mTORC1 is actived by checking if its downstream target p70S6K is phosphorylated on Ser 371 and Thr 389, in western blot.
I know that mTORC1 is activated by nutrients, in particular aminoacids, and growth factors such insulin.
Aminonoacids stimulate TORC1 through a process involving the translocation of TORC1 to lysosomal membranes by the Regulator-Rag complex and Phospholipase D1.
Insulin stimulate TORC1 through activation of PI3K kinase by the adaptor insulin-receptor substrate (IRS). PI3K produces PIP3, which activates the Kinase AKT. This latter inhibits the dimer TSC1/TSC2, alleviating its repression of Rheb and so stimulating TORC1 activity.
I'm sorry but I can't tell you more about.
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