| First Author | Dennis MD | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 1 | Pages | 10-9 |
| PubMed ID | 23184952 | Mgi Jnum | J:244821 |
| Mgi Id | MGI:5913600 | Doi | 10.1074/jbc.M112.402461 |
| Citation | Dennis MD, et al. (2013) Mechanistic target of rapamycin complex 1 (mTORC1)-mediated phosphorylation is governed by competition between substrates for interaction with raptor. J Biol Chem 288(1):10-9 |
| abstractText | In this study, the interaction of mTORC1 with its downstream targets p70S6K1 and 4E-BP1 was evaluated in both mouse liver and mouse embryonic fibroblasts following combined disruption of the genes encoding 4E-BP1 and 4E-BP2. Phosphorylation of p70S6K1 was dramatically elevated in the livers of mice lacking 4E-BP1 and 4E-BP2 following feeding-induced activation of mTORC1. Immunoprecipitation of mTORC1 suggested that elevated phosphorylation was the result of enhanced interaction of p70S6K1 with raptor. These findings were extended to a cell culture system wherein loss of 4E-BP1 and 4E-BP2 resulted in elevated interaction of p70S6K1 with IGF1-induced activation of mTORC1 in conjunction with an enhanced rate of p70S6K1 phosphorylation at Thr-389. Furthermore, cotransfecting HA-p70S6K1 with 4E-BP1, but not 4E-BP1(F114A), reduced recovery of mTORC1 in HA-p70S6K1 immunoprecipitates. Together, these findings support the conclusion that, in the absence of 4E-BP proteins, mTORC1-mediated phosphorylation of p70S6K1 is elevated by a reduction in competition between the two substrates for interaction with raptor. |
