Key kinase downstream of PI3K in growth signaling; activated by mTORC2.
| Tier | What it means | Studies |
|---|---|---|
| D | Mechanistic / in vitro / review | 10 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or mechanistic work.
| Study | Year | Tier | Finding |
|---|---|---|---|
| FEL2009 | 2009 | D | The parallel discovery to Thoreen 2009 (same year), from the Shokat lab. Their TORKinibs (PP242, PP30) block mTOR's active site, hitting both complexes and shutting down cap-dependent translation that |
| PET2009 | 2009 | D | Identified DEPTOR as a built-in brake on BOTH mTOR complexes. The twist: in some multiple myelomas DEPTOR is overexpressed, which by relieving a feedback loop actually keeps pro-survival Akt signaling |
| SAN2007 | 2007 | D | Identified PRAS40 as the missing insulin-controlled brake INSIDE mTORC1. When insulin is absent PRAS40 clamps the complex shut; insulin makes Akt phosphorylate PRAS40, releasing the brake so Rheb can |
| GUE2006 | 2006 | D | The definitive genetic 'dissection' of the two complexes in living mice. Deleting Raptor was lethal early (mTORC1 essential); deleting Rictor or mLST8 selectively knocked out mTORC2 signaling to Akt a |
| SAR2006 | 2006 | D | The molecular explanation for rapamycin's dark side. Short-term rapamycin only hits mTORC1, but LONG-term treatment also strips down mTORC2 in many cells, cutting Akt signaling. This is the mechanisti |
| SAR2005 | 2005 | D | The rictor-mTOR complex (mTORC2) directly phosphorylates Akt/PKB on Ser473, regulating cell survival. |
| SAR2004 | 2004 | D | Discovery of Rictor and the SECOND mTOR complex, mTORC2. Crucially showed this complex is NOT blocked by rapamycin and does not use Raptor - it controls the cytoskeleton via PKC. This is the paper tha |
| CAN2002 | 2002 | D | Review establishing PI3K as a central signaling hub controlling cell survival, metabolism, and growth downstream of growth-factor receptors and upstream of Akt and mTOR. |
| INO2002 | 2002 | D | Akt directly phosphorylates and inactivates TSC2, disrupting the TSC1-TSC2 complex and releasing its inhibition of mTOR - the link between growth-factor/insulin signaling and mTORC1 activation. |
| ROM2001 | 2001 | D | Shows IGF-1 drives muscle fiber hypertrophy specifically through the Akt-mTOR pathway, establishing mTORC1 as a central node for muscle growth signaling. |