IndraLab
Statements
sparser
"However, neither ERK1/2 activity, as indicated by phosphorylation of their activation loop (Thr202/Tyr204 of ERK1 and Thr183/Tyr185 of ERK2), nor activity of the mTOR pathway, as indicated by phosphorylation of 4E binding protein 1 (4E-BP) and the ribosomal protein S6, were significantly correlated with the low LC3-II levels ( xref )."
sparser
"Using different AML cell lines (U937, MM6 and Kasumi-1), we analyzed the effects of these agents on the phosphorylation of AKT on serine 473 (Ser473), a marker of mTORC2 activity, and the phosphorylation of S6 ribosomal protein (rpS6) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), markers of mTORC1 activity."
sparser
"However, constitutive enhanced levels of Akt activity may obstruct both ATR/Chk1 signaling and homologous recombination repair (HRR), either by direct phosphorylation of Chk1 and/or DNA topoisomerase 2-binding protein 1 (TopBP1) or via prevention of assembly to the sites of DNA damage of double-strand break (DSB) resection factors, such as breast cancer susceptibility gene 1 (Brca1), replication protein A (RPA), and Rad51 [ xref , xref – xref ]."
sparser
"Ang II stimulated protein synthesis and cell hypertrophy in AT1R/Cl4 cells without increasing cell number, and signaling studies revealed that Ang II stimulated phosphorylation of the 40S ribosomal protein S6 and the eukaryotic translation initiation factor 4E-binding protein 1, the two downstream target proteins of the mammalian target of rapamycin, which is a central regulator of protein synthesis and cell size."
sparser
"The requirement of the PI3K/Akt pathway in TGF-β-mediated EMT could be mediated, at least in part, by a downstream effector of Akt, mammalian target of rapamycin (mTOR), which is a key regulator of protein synthesis via phosphorylation of S6 kinase (S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1)."
sparser
"mTOR has an important role in cell growth and proliferation by phosphorylating p70 ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP-1), which subsequently promotes ribosomal biogenesis and the mRNA translation of proteins that are required for cell proliferation xref ."
sparser
"Recently, we have shown that curcumin inhibits phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), two downstream effector molecules of the mammalian target of rapamycin complex 1 (mTORC1) in numerous cancer cell lines."
sparser
"It is a serine-threonine kinase that, upon activation, phosphorylates the ribosomal protein S6 kinase [ xref ] and the eukaryotic initiation factor 4E binding protein 1 (4E-BPI) [ xref ], which promotes ribosome biogenesis and induces the translation of proteins involved in cell cycle progression and proliferation [ xref - xref ]."
sparser
"Accordingly, the activity of the mTOR signalling, which negatively modulates autophagy and is known to be inhibited by AMPK, was downregulated when treated with FK506, as represented by decreased phosphorylation of mTOR (Ser2448) and its two primary downstream targets p70 ribosomal protein S6 kinase (p70S6K; Thr389) and elongation factor 4E binding protein 1 (4E-BP1; Thr37/46)."
sparser
"We found that fibronectin stimulated the phosphorylation of Akt, an upstream inducer of mTOR, and induced the phosphorylation of p70S6K1 and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), two downstream targets of mTOR in NSCLC cells (H1792 and H1838), whereas it inhibited the phosphatase and tensin homologue deleted on chromosome 10, a tumor suppressor protein that antagonizes the phosphatidylinositol 3-kinase/Akt signal."
sparser
"Concordant with the inactivation of mTORC1, phosphorylation of the mTORC1 substrates eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and p70 ribosomal protein S6 kinase 1 (p70S6K1) was reduced in response to live compared to dead L. innocua , indicating repression of protein translation ( xref and xref )."
sparser
"The regulation of cap-dependent translation initiation by mTOR involves direct phosphorylation of its substrates eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and ribosomal protein kinase S6 (p70S6K). xref , xref Activated p70S6K phosphorylates the 40S ribosomal protein S6 whereas phosphorylation of 4E-BP1 disrupts its inhibitory interaction with eukaryotic initiation factor 4E (eIF-4E)."
sparser
"mTORC1 is sensitive to energy, amino acids, growth factors, and oxygen levels, as well as rapamycin, regulates phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), and controls protein and lipid synthesis, cell growth, proliferation, survival and motility [ xref - xref , xref - xref ]."
sparser
"Interestingly, despite inhibition of phosphorylation of AKT at 6 hours following treatment administration, prolonged therapy resulted in persistently decreased phosphorylation of ribosomal protein S6 (RPS6) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), but AKT phosphorylation was restored ( xref )."
sparser
"As shown in xref , acute arsenic treatment inhibited MTOR evidenced by decreased phosphorylation of MTOR as well as its substrates eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1 or EIF4EBP1) and P70S6 kinase (P70S6K), and the inhibition was reduced upon prolonged arsenic exposure."
sparser
"• Figures 1 (both panels), 3A, 3B, 3D, 3E, 4A, and 8A in: Aronica, S.M., Gingras, A.C., Sonenberg, N., Cooper, S., Hague, N., & Broxmeyer, H.E. “Macrophage Inflammatory Protein-1 α and Interferon-inducible Protein 10 Inhibit Synergistically Induced Growth Factor Stimulation of MAP Kinase Activity and Suppress Phosphorylation of Eukaryotic Initiation Factor 4E and 4E Binding Protein 1.” Blood 89:3582-3595, 1997 (May 15) (“ Blood paper”)."
sparser
"mTORC1 regulates phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), and controls protein and lipid synthesis, cell growth, proliferation, survival and motility ( xref ; xref ; xref ; xref ; xref ; xref ), while mTORC2 regulates phosphorylation or activity of Akt, serum and glucocorticoid-induced kinase 1 (SGK1), protein kinase C α (PKCα), focal adhesion proteins and small GTPases, and controls cell survival and actin cytoskeleton ( xref ; xref )."
sparser
"Of interest, in contrast to the effects of conventional mTOR inhibitors (rapalogs), DHA potently inhibited mTORC1-mediated phosphorylation of p70 S6 kinase 1 and eukaryotic initiation factor 4E binding protein 1 but did not obviously affect mTORC2-mediated phosphorylation of Akt."
sparser
"• Aronica, S.M., Gingras, A.-C., Sonenberg, N., Cooper, S., Hague, N., and Broxmeyer, H.E. “Macrophage Inflammatory Protein-1 α and Interferon-Inducible Protein 10 Inhibit Synergistically Induced Growth Factor Stimulation of MAP Kinase Activity and Suppress Phosphorylation of Eukaryotic Initiation Factor 4E and 4# Binding Protein 1.” Blood 89:3582-3595, 1997."
sparser
"This translational regulation results from activation by TGF-β of mammalian target of rapamycin (mTOR) through phosphatidylinositol 3-kinase and Akt, leading to the phosphorylation of S6 kinase 1 and eukaryotic initiation factor 4E–binding protein 1, which are direct regulators of translation initiation."
sparser
"In contrast,
mTORC1, a key regulator of translation in response to the cell’s nutrient
status and growth factor signals ( xref ; xref ), was profoundly inhibited by HIF-mediated acidification as
indicated by reduced phosphorylation of ribosomal protein S6 and its kinase
(S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1)
( xref , xref )."
sparser
"It can be regulated upstream by growth factors (GFs), the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, and the nutrient/5′ adenosine monophosphate-activated protein kinase (AMPK) pathway, and it regulates downstream pathways including those involving stabilizing HIFs and those promoting cap-dependent translation through the phosphorylation of S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) ( xref , xref )."
sparser
"Here we show that CPX inhibited the phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), two downstream effector molecules of mTOR complex 1 (mTORC1), in a spectrum of human tumor cells, indicating that CPX inhibits mTORC1 signaling."
sparser
"Using this technology, a study of formalin-fixed paraffin-embedded (FFPE) specimens from a cohort of over 700 colorectal cancer patients demonstrated considerable differences in the phosphorylation of two proteins, ribosomal protein S6 (S6) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), in individual cells within tissue microarray tissue cores ( xref )."
sparser
"Recent studies have revealed that Akt also regulates the protein translation process by direct phosphorylation of the mammalian target of rapamycin (mTOR) ( xref ), which in turn regulates protein synthesis through phosphorylating 4E binding protein 1 (4E-BP1) and p70 ribosomal protein S6 kinase (S6K1) ( xref - xref )."
sparser
"AZD8055 ( xref ) is a prototypic, orally-available, ATP-competitive mTOR kinase inhibitor, that suppresses phosphorylation of the mTORC1 substrates p70S6K and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), as well as phosphorylation of the mTORC2 substrate AKT (S473)."
sparser
"Branched-chain amino acids regulate mammalian target of rapamycin (mTOR), which has been implicated as a nutritional sensor, that regulates cell growth and protein synthesis via increased rates of mRNA translation through the phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and the ribosomal protein S6 kinase 1 [ xref , xref , xref ]."
sparser
"We have identified phosphorylation of splicing factor Y-box Protein 1 (YBX1) by mutated JAK2 as a critical downstream event that is essentially required for mRNA splicing of the ERK-signaling component Mitogen-activated Protein Kinase Interacting Serine/Threonine Kinase 1 (MKNK1)."
sparser
"After exposure to dexamethasone (DEX, 100 μmol/l) for 24 h, protein synthesis in muscle cells was significantly suppressed ( P <0.05), the phosphorylations of mTOR, ribosomal protein S6 protein kinase 1 (p70s6k1) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) were significantly reduced ( P <0.05)."
sparser
"The mTORC1 activity is regulated by upstream signals from growth factors, amino acids, stresses and energy state, and its activation induces the phosphorylation of p70S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), leading to the enhanced translation of a subset of mRNAs that are critical for cell growth and metabolism [ xref , xref ] ( xref )."
sparser
"Activated mTORC1 mediates the phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinases (S6K), resulting in the release of eukaryotic translation initiation factor 4E (eIF4E) and phosphorylation of S6 [ xref , xref ] (Figure xref )."
sparser
"Subsequently, activated PI3K or Akt may positively regulate mTOR, leading to increased phosphorylation of ribosomal p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), the two best-characterized downstream effector molecules of mTOR [ xref , xref ]."
sparser
"Signalling through AKT inhibits the upstream inhibitor of MTORC1, thereby inducing MTORC1 activation and subsequent phosphorylation of its downstream targets eukaryotic translation initiation factor 4E‐binding protein 1 (EIF4EBP1, also called 4EBP1) and ribosomal protein S6 kinase, 70kDa, polypeptide 1 (PRPS6KB1, also called p70S6K). xref The increased AKT activation in the limb muscle of cachectic patients compared with non‐cachectic COPD patients is paralleled by an increase in phosphorylation of the downstream targets 4E‐BP1 and p70S6K. xref P70S6K phosphorylation is unaltered in COPD patients compared with controls, xref while ribosomal protein S6 (RPS6 referred to as S6) phosphorylation was even decreased in COPD patients. xref Together, these studies show an increase in protein synthesis signalling in the limb muscles of cachectic COPD patients compared with non‐cachectic COPD patients, but no alteration in the general COPD population."
sparser
"It was observed that Torin1 inhibited the phosphorylation of AKT (Ser473), p70 ribosomal S6 kinase 1 (S6K1, Thr389), S6 ribosomal protein (Ser235/236), and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1, Thr37/46), which are used for measurement of mTOR activity."
sparser
"Since phosphorylation of S6 at Ser235/236 sites is regulated by both mTORC1 and mitogen-activated protein kinases xref we confirmed mTORC1 involvement by western blot analyses and showed decreased expression of pRAPTOR (Ser792) and increased phosphorylation of S6 (Ser235/236; pS6/S6 ratio: 12.3±1.9 mutant/8.2±1.9 control) and eukaryotic translation initiation factor 4E-Binding Protein 1 (4EBP1, Thr37/46; p4EBP1/4EBP1 ratio: 0.8±0.0 mutant/0.5±0.1 control) in the mutant oviducts (n = 3) ( xref )."
sparser
"When tuberin and/or hamartin are absent or nonfunctional, mTOR is constitutively active and its downstream effectors, p70 S6 kinase (S6K), S6 ribosomal subunit (S6) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) are hyperphosphorylated, which results in increased cell growth, cell proliferation, and survival[ xref , xref ]."
sparser
"The mTORC1 regulates translation initiation by phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1, and functions primarily in the control of a large array of cellular processes, including cell proliferation, growth, differentiation and survival ( xref )."
sparser
"Phosphorylation of S6 ribosomal protein (pS6) and 4E binding protein 1 (p4EBP1), the downstream targets of mTOR xref , and proliferating cell nuclear antigen (PCNA) was significantly increased in pancreas of the Neurog3 - Tsc1 −/− (TN) mice relative to the control littermates (WT)."
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"Further validation of the TNF/Fas/TRAIL pathway was performed in ALK(+) anaplastic large cell lymphoma (ALCL) cell lines with knockdown of NPM-ALK using short interference RNA, resulting in the loss of the tyrosine phosphorylation of tumor necrosis factor receptor-associated protein 1 (TRAP1) and receptor-interacting protein 1, two crucial TNF signaling molecules."
sparser
"mTOR ( xref ) is a component of two similar complexes: mTORC1, which promotes mRNA translation and protein synthesis by the phosphorylation of ribosomal protein S6 kinase (S6K1) and eIF4E binding protein 1 (4E-BP1) and mTORC2, which organizes the cellular actin cytoskeleton and regulates Akt phosphorylation ( xref )."
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"We evaluated differences in activation of the PI3K/AKT/mTOR pathway in estrogen receptor α (ERα) positive primary and corresponding metastatic breast cancer tissues using immunohistochemistry for downstream activated proteins, like phosphorylated mTOR (p-mTOR), phosphorylated 4E Binding Protein 1 (p-4EBP1) and phosphorylated p70S6K (p-p70S6K)."
sparser
"In order to examine whether NUAK1 influences mTOR phosphorylation and induces the phosphorylation of p70S6K1 and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), two downstream targets of mTOR in NSCLC cell ( xref ), western blot was performed to analyse the EGF-induced phosphorylation of mTOR pathway."
sparser
"Activation of mTOR downregulates autophagy and leads to the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4EBP1) and 70 kDa polypeptide 1 ribosomal protein S6 kinase-1 (p70S6K). xref We monitored the activity of mTOR by detecting the levels of phosphorylation of its substrate, p4EBP1, and found that it was negatively correlated with the level of autophagy, which means the inhibition of mTOR signaling."
sparser
"Furthermore, the compensatory increase in Unc51 like autophagy activating kinase 1 possibly competes with eukaryotic initiation factor 4E-binding protein 1 and ribosomal p70 S6kinase phosphorylation by mechanistic targets of rapamycin complex 1 to uncouple its effect on protein synthesis."
sparser
"Interestingly, LaRocca et al. showed that the binding of pore-forming toxins to human CD59 (hCD59) may trigger a third pathway of red blood cell (RBC) death, which shares key molecular factors with nucleated cell necroptosis, including dependence on Fas/FasL signaling and Receptor-Interacting Protein 1 (RIP1) phosphorylation."
sparser
"Activation of mTORC1 mainly lead to the phosphorylation of two downstream targets, p70 ribosomal S6 kinase/S6 ribosomal protein (p70S6K/S6RP) and eukaryotic translation-initiation factor 4E–binding protein 1 (4E–BP1), enhancing protein synthesis from increased ribosome biogenesis and messenger RNA translation under nutrient-rich conditions, promoting lipid biogenesis, and inhibiting autophagy [ xref ].."
sparser
"Subsequently, activated PI3K or Akt may positively regulate mTOR, leading to increased phosphorylation of ribosomal p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), the two best-characterized downstream effector molecules of mTOR [ xref - xref ]."
sparser
"Akt/mTOR signaling pathway has been well-known to play critical roles in controlling cell proliferation and apoptosis as well as autophagy induction through modulation of protein translation via phosphorylation of p70 ribosomal protein S6 kinase (p70 S6K) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1)."
sparser
"In physiological settings, mTORC1 senses diverse intracellular and extracellular cues, including signals of growth factors and amino acids, and regulates various cellular activities through phosphorylating eukaryotic translation initiation factor 4E (eIF4E) binding protein 1 (4E-BP1) and S6 kinase 1 (S6K1), which are critical for protein synthesis and ribosome biogenesis [ xref – xref ]."
sparser
"mTOR lies downstream of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt/PKB), so activated Akt may positively regulate mTOR, leading to increased phosphorylation of ribosomal p70S6 kinase (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), two best characterized downstream effector molecules of mTOR [ xref ]."
sparser
"The activated Phosphoinositide 3-kinase (PI3K)/AKT pathway stimulates mTOR to phosphorylate its downstream effectors p70 ribosomal S6 kinase (p70S6K) and eukaryotic initiation factor 4E binding protein 1 (4EBP1), mediating the expression of genes associated with tumor malignancy xref , xref ."