| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
120-264 |
DRI_Outcome |
denotes |
The tuberous sclerosis gene products Tsc1 and Tsc2 behave as tumor suppressors by restricting cell growth, a function conserved among metazoans. |
| T2 |
265-444 |
DRI_Background |
denotes |
Recent evidence has indicated that hyperactivation of S6 kinase 1 (S6K1) may represent an important biochemical change in the development of tuberous sclerosis-associated lesions. |
| T3 |
445-751 |
DRI_Outcome |
denotes |
We show here that deletion of either Tsc1 or Tsc2 or expression of the Rheb (Ras homolog enriched in brain) GTPase leads to hyperphosphorylation of S6K1 at a subset of regulatory sites, particularly those of two essential residues functionally conserved among AGC superfamily serine/threonine kinases, i.e. |
| T4 |
752-835 |
DRI_Approach |
denotes |
the activation loop (T-loop; Thr-229) and the hydrophobic motif (H-motif; Thr-389). |
| T5 |
836-948 |
DRI_Approach |
denotes |
These sites are reciprocally and dose-dependently regulated when S6K1 is coexpressed with the Tsc1-Tsc2 complex. |
| T6 |
949-1101 |
DRI_Outcome |
denotes |
Mutations that render S6K1 mTOR (mammalian target of rapamycin)-resistant also protect S6K1 activity and phosphorylation from down-regulation by Tsc1/2. |
| T7 |
1102-1277 |
DRI_Outcome |
denotes |
We demonstrate that two disease-associated mutations in Tsc2 fail to negatively regulate S6K1 activity concomitant with a failure to modify T-loop and H-motif phosphorylation. |
| T8 |
1278-1463 |
DRI_Challenge |
denotes |
Finally, we identify one pathological Tsc2 mutation that retains its ability to negatively regulate S6K1, suggesting that, in some cases, tuberous sclerosis may develop independently of |
| T9 |
1484-1485 |
DRI_Challenge |
denotes |
. |
