E-viri
Recenzirano
Odprti dostop
-
Menon, Suchithra; Dibble, Christian C.; Talbott, George; Hoxhaj, Gerta; Valvezan, Alexander J.; Takahashi, Hidenori; Cantley, Lewis C.; Manning, Brendan D.
Cell, 02/2014, Letnik: 156, Številka: 4Journal Article
mTORC1 promotes cell growth in response to nutrients and growth factors. Insulin activates mTORC1 through the PI3K-Akt pathway, which inhibits the TSC1-TSC2-TBC1D7 complex (the TSC complex) to turn on Rheb, an essential activator of mTORC1. However, the mechanistic basis of how this pathway integrates with nutrient-sensing pathways is unknown. We demonstrate that insulin stimulates acute dissociation of the TSC complex from the lysosomal surface, where subpopulations of Rheb and mTORC1 reside. The TSC complex associates with the lysosome in a Rheb-dependent manner, and its dissociation in response to insulin requires Akt-mediated TSC2 phosphorylation. Loss of the PTEN tumor suppressor results in constitutive activation of mTORC1 through the Akt-dependent dissociation of the TSC complex from the lysosome. These findings provide a unifying mechanism by which independent pathways affecting the spatial recruitment of mTORC1 and the TSC complex to Rheb at the lysosomal surface serve to integrate diverse growth signals. Display omitted •Insulin triggers acute dissociation of the TSC complex from Rheb at the lysosome•Release of the TSC complex from the lysosome is required to activate mTORC1•Dissociation of TSC complex from the lysosome requires Akt phosphorylation of TSC2•The TSC complex is constitutively dissociated from the lysosome in PTEN null cells Activation of the PI3K-Akt pathway signals to mTORC1 by stimulating release of the TSC complex from Rheb at the lysosomal surface, where mTORC1 is independently recruited through amino acid sensing mechanisms. This spatial regulation provides a mechanism to integrate growth signals upstream of mTORC1.
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.