IndraLab
Statements
reach
"We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain and substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR and PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites."
reach
"A central event of this signaling
cascade is the phosphorylation of protein kinase B (PKB) on its Thr308
residue (by PDK1) and Ser473 (by mTORC2), resulting in kinase activation
and subsequent phosphorylation of multiple downstream targets, such
as PRAS40, an inhibitory binding partner for mammalian target of rapamycin
(mTOR)."
sparser
"Previous studies have primarily focused on the regulation of pathways such as EGFR, HIF-α-VEGF, Rab11-FIP4, mTOR-PRAS40, and the transcription factor NF-κB. However, interventions targeting these pathways have not effectively curbed liver cancer cell invasion and metastasis, suggesting the existence of other critical regulatory pathways and mechanisms xref , xref ."
sparser
"In addition, 14-3-3 proteins may associate with Raptor and ULK1 under conditions of nutrient deprivation and phosphorylation-dependent 14-3-3 association with Raptor may reduce the availability of 14-3-3 for PRAS40 binding, which may have the combined effect of suppressing mTOR kinase activity and inducing autophagy."
reach
"Akt phosphorylation by PDK1 carries out two events: the inactivation of the GTPase tuberous sclerosis protein (TCS)1/2 complex, which allows the Ras homolog enriched in the brain (Rheb) to accumulate in a GTP-bound form capable of binding to mTOR (71), and the disassociation of the inhibitor PRAS40 from Raptor, both of which events allow the activation of mTORC1 (72)."