IndraLab

Statements


10 1 | 1 36 32

reach
"Mechanistically, miR-96 targeted the 3 '-UTR (3 '-untranslated region) of AKT1S1 mRNA leading to its downregulation and disruption of the AKT1S1 and mTOR complex."

sparser
"When PRAS40 is bound to mTOR, mTOR activity is reduced; in contrast, when mTOR detaches from PRAS40, mTOR is active ( xref )."

reach
"34 In mTORC1, Raptor acts as a bridge to PRAS40, whereas PRAS40 and mLST8 bind to mTOR as negative and positive regulatory subunits, respectively."

sparser
"DEPTOR is unique among the mTOR binding proteins in that it associates with both the mTORC1 and -2, and unlike PRAS40 interacts directly with the mTOR protein."

sparser
"Three main signaling axes were identified for the downregulated phospho-proteins, namely, CHK2-TP53, PRAS40-MTOR and SRC family kinases ( xref B)."

reach
"Unlike DEPTOR, which inhibits both mTORC1 and mTORC2, PRAS40 (proline rich Akt substrate 40 kDa) binds the mTOR kinase domain in a phosphorylation dependent manner and only suppresses the kinase activity of mTORC1 [XREF_BIBR, XREF_BIBR]."

sparser
"Furthermore, PRAS40 binding to mTOR was strongly reduced when Raptor was knocked down ( xref )."

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
"Such evidence suggests multiple protein–protein interactions between PRAS40 and both mTOR and Raptor."

reach
"The phosphorylation of PRAS40 by AKT leads to a disruption of the interaction between PRAS40 and mTOR that results in an increase in mTOR kinase activity ( Fig. 3 A) ( Lin et al., 2020 )."

sparser
"Additionally, AKT directly phosphorylates AKT1S1 (PRAS40), and this phosphorylation acts to block the inhibitory binding of AKT1S1 to FRAP1 [ xref ]."

reach
"To our surprise, the binding of PRAS40 to mTOR was reduced even though PRAS40 phosphorylation on Thr246 was ablated in response to cAMP (XREF_FIG A)."

reach
"MTOR is found in two separate multiprotein complexes : mTOR complex (mTORC) 1, in which mTOR interacts with raptor, mLST8, and PRAS40; and mTORC2, formed by mTOR interaction with rictor, mLST8, and mSin."

reach
"The PRAS40-beta5i interaction still occurred in the presence of Triton X100 (XREF_FIG), the detergent that disrupts the PRAS40-mTOR and raptor interaction, indicating that PRAS40 can bind to beta5i without mTOR and raptor."

reach
"The difference between Torin1 and rapamycin could also be due to the effect of rapamycin in perturbing the interaction between PRAS40 and mTOR and raptor, as revealed previously."

sparser
"Genetic investigation of the factors associated with PRAS40 induction during mTOR inhibition identified amplification of EGFR, MDM2, and PDGFRA as more common in the non-responder subgroup, a finding not predicted from preclinical work."

sparser
"Rapamycin is known to weaken the interaction of mTOR–Raptor complexes [32] so it was suggested that the decrease in PRAS40mTOR affinity following rapamycin treatment was caused through destabilisatio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Indeed, high levels of pPRAS40 have been associated with high mTOR activity [ xref , xref ]."

sparser
"To our surprise, the binding of PRAS40 to mTOR was reduced even though PRAS40 phosphorylation on Thr246 was ablated in response to cAMP ( xref A)."

sparser
"These results suggest that MKP7 could directly dephosphorylate pmTOR and pPRAS40 and forming complexes with these two proteins ( xref )."

reach
"Researchers illustrated that under basal conditions PRAS40 binds to mTOR to inactivate it, and that mTOR inactivation is relieved when insulin stimulation activates AKT to phosphorylate PRAS40, thereby initiating release from mTOR."

sparser
"The interaction of PRAS40 with the mTOR complex 1 (mTORC1) inhibits the activity of mTORC1."

sparser
"The dephosphorylated mTOR and PRAS40 formed a complex resulting in quiescent mTOR activity."

sparser
"Whereas one report indicated that PRAS40 binds to the mTOR catalytic domain [28] , a second report showed that Raptor was required for stable association of PRAS40 with mTOR, consistent with the mTORC[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The interaction between mTOR and PRAS40 is disrupted by rapamycin, indicating that FKBP12 may mediate its nascent inhibitory activity [XREF_BIBR, XREF_BIBR - XREF_BIBR]."

reach
"A newly resolved crystal structure of Arabidopsis mTORC1 shows direct binding of PRAS40 to mTOR at multiple residues including the rapamycin binding pocket [XREF_BIBR]."

reach
"MTORC1 is comprised of mTOR, mLST8, and RAPTOR alongside the accessory inhibitory factors PRAS40 and DEPTOR, which bind mTORC1 via RAPTOR and mTOR, respectively (Figure 1)."

sparser
"PRAS40 also binds mTOR to transduce Akt signals to the mTOR complex."

sparser
"Inhibition of mTOR signaling stimulates PRAS40 binding to mTOR, which in turn inhibits mTOR activity."

sparser
"In the presence of EtOH, there was an increased interaction between PRAS40 and mTOR."

reach
"As dephosphorylated PRAS40 is known to inhibit mTORC1 by direct binding [XREF_BIBR], we predicted that PRAS40 could also interact with mTOR in this same subcellular compartment."

sparser
"This is consistent with reports in which stressors such as amino acid deprivation or the glycolytic inhibitor 2-deoxyglucose increased the PRAS40-mTOR interaction [ xref ]."

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)."

reach
"Additionally, AKT directly phosphorylates AKT1S1 (PRAS40), and this phosphorylation acts to block the inhibitory binding of AKT1S1 to FRAP1 [XREF_BIBR]."

reach
"PraS40 is bound to mTOR by Raptor to exert its inhibitory effect on mTORC1 protein kinase activity [ 60 ]."

reach
"MTOR interaction with Raptor, mLST8 and GbetaL, and PRAS40 forms the mTORC1 complex."

sparser
"Treatment with the iron chelators consistently increased the binding of PRAS40 to mTOR, which was attenuated by FeSO 4 pretreatment in all cases (Fig. xref )."

reach
"In human cells, PRAS40 binds to mTOR in an insulin dependent manner and may act as a negative regulator of TORC1 in the absence of insulin."

sparser
"These results suggest that the effect of iron chelation on the PRAS40-mTOR interaction is consistent, but its effect on the raptor-mTOR interaction is cell line dependent."

reach
"In the presence of EtOH, there was an increased interaction between PRAS40 and mTOR."

sparser
"To verify whether AMPK mediates increased p-raptor (S792) or PRAS40 binding to mTOR, IP against mTOR was performed after cells were treated with CPX or Dp44mT, with/without Compound C pretreatment."

sparser
"Increased p-raptor (S792) or PRAS40 binding to mTOR was inhibited by Compound C (Figs. xref and xref ), suggesting that AMPK mediates iron chelation-increased p-raptor/PRAS40 binding to mTOR."

sparser
"As dephosphorylated PRAS40 is known to inhibit mTORC1 by direct binding [ xref ], we predicted that PRAS40 could also interact with mTOR in this same subcellular compartment."

reach
"AKT1S1 (PRAS40) binds the mTOR kinase domain and inhibits mTORC1 mediated signalling."

reach
"In this case the inhibtion of phosphorylation leads to release of 14-3-3 proteins, inducing binding of AKT1S1 to mTOR and inhibition of function."

sparser
"AMPK phosphorylation of Raptor is thought to lead to changes in the availability of 14-3-3 for PRAS40 binding, which acts to suppress mTOR kinase activity, thus leading to autophagy initiation."

reach
"Treatment with the iron chelators consistently increased the binding of PRAS40 to mTOR, which was attenuated by FeSO 4 pretreatment in all cases."

reach
"To verify whether AMPK mediates increased p-raptor (S792) or PRAS40 binding to mTOR, IP against mTOR was performed after cells were treated with CPX or Dp44mT, with and without Compound C pretreatment."

reach
"Increased p-raptor (S792) or PRAS40 binding to mTOR was inhibited by Compound C (Figs."

reach
"XREF_FIG and S5B, C), suggesting that AMPK mediates iron chelation increased p-raptor and PRAS40 binding to mTOR."

reach
"When PRAS40 is bound to mTOR, mTOR activity is reduced; in contrast, when mTOR detaches from PRAS40, mTOR is active (Saxton and Sabatini, 2017)."

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
"The interaction between mTOR and PRAS40 is disrupted by rapamycin, indicating that FKBP12 may mediate its nascent inhibitory activity [ xref , xref – xref ]."

sparser
"A newly resolved crystal structure of Arabidopsis mTORC1 shows direct binding of PRAS40 to mTOR at multiple residues including the rapamycin-binding pocket [ 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
"PRAS40 also binds mTOR to transduce Akt signals to the mTOR complex."

reach
"Inhibition of mTOR signaling stimulates PRAS40 binding to mTOR, which in turn inhibits mTOR activity."

reach
"We noticed that PRAS40 is a downstream target and negative regulator of mTOR activity, PRAS40 binds the mTOR kinase domain, thus inhibits mTOR activity [51], These findings identify PRAS40 as an impor[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Furthermore, PRAS40 binding to mTOR was strongly reduced when Raptor was knocked down (XREF_FIG)."

sparser
"PIM1 protein kinase overexpression reduced the association of PRAS40 with mTOR, and increased the mTOR directed phosphorylation of 4EBP1 and p70S6Kinase."

sparser
"PRAS40 dephosphorylation is associated with the inhibition of mTOR activity in renal cancer cells [ xref ]."

sparser
"Similarly, phosphorylation of p70S6K is also restored by IGF1 stimulation in gefitinib-treated cells, suggesting that the well-known interaction of PRAS40 with mTOR could explain the resistance phenomenon."

reach
"PRAS40 binds the mTOR kinase domain and its interaction with mTOR is induced under conditions that inhibit mTOR signalling, such as nutrient or serum deprivation or mitochondrial metabolic inhibition."

reach
"In co-immunoprecipitation assays, antibody against mTOR pulled down PRAS40 and MKP7, while antibody against PRAS40 pulled down MKP7, suggesting the interaction of mTOR and PRAS40 with MKP7."

trips
"PRAS40 binds the mTOR kinase domain and its interaction with mTOR is induced under conditions that inhibit mTOR signalling, such as nutrient or serum deprivation or mitochondrial metabolic inhibition."

sparser
"These results suggest that 14-3-3η may be involved in promoting tumorigenesis in pituitary oncocytoma by interacting with PRAS40 (T246) via the mTOR signaling pathway."

reach
"The binding of mTOR, PRAS40 and RagC to raptor did not differ for control and septic muscle in the basal condition; however, the Leu induced decrease in PRAS40 * raptor and increase in RagC * raptor seen in control muscle was absent in sepsis."

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)."

sparser
"In this case the inhibtion of phosphorylation leads to release of 14-3-3 proteins, inducing binding of AKT1S1 to mTOR and inhibition of function."