IndraLab
Statements
sparser
"A recent study
[ xref ] indicated that MCPyV -ST expression was required for the Merkel cell tumor growth in vitro and was observed to act downstream in the mammalian target of rapamycin (mTOR) signaling pathway to preserve eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) hyperphosphorylation, resulting in dysregulated cap-dependent translation and that 4E-BP1 inhibition is required for MCPyV transformation."
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
"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
"As has been shown recently using the other biochemical approaches, G α i1 and G α i3 form the complex with ligand-activated EGF receptor and are required for phosphorylation of Grb2-associated binding protein 1 and its subsequent interaction with p85 subunit of PI3-K in response to EGF, whereas the coupling between EGF receptor and G s protein leads to activation of cAMP-dependent signaling pathways [ xref , xref ]."
sparser
"Temsirolimus and everolimus, termed rapalogs, have been used as first‐generation mTOR inhibitors for first‐line or second‐line therapy against advanced RCC. xref mTOR is present in 2 complexes, mTORC1 and mTORC2. xref , xref The function of mTORC1 is mediated by phosphorylation of eukaryotic translation initiation factor 4E‐binding protein 1 (4EBP1) and p70S6K, promoting mRNA translation and cell proliferation."
sparser
"mTOR complex 1 (mTORC1), which contains mTOR, Raptor, mammalian lethal with SEC13 protein 8 (mLST8) and proline-rich Akt substrate 40 (PRAS40) [ xref , xref ], regulates aberrant energy homeostasis through phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) [ xref , xref – xref ]."
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
"Similar to sodium butyrate (NaB, a histone deacetylase inhibitor), ORI significantly increased p38 mitogen‑activated protein kinase (MAPK) activation, γ‑globin expression, histone H3 and H4 acetylation at the Gγ‑ and Aγ‑globin promoters, and cAMP‑response element binding protein 1 (CREB1) phosphorylation."
sparser
"In pro-BII cells of patients who ultimately relapsed, we observed high basal activity of rpS6 and a lack of response to pervanadate, as assessed by phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p4EBP1), due to high basal activation of 4EBP1 ( xref , left; xref )."
sparser
"In parallel, glycogen synthase kinase 3beta (GSK-3beta) inactivation and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation were monitored as markers of the rapamycin-insensitive and -sensitive branches of the PI3K signaling pathway, respectively."
sparser
"Moreover, the mammalian target of rapamycin (mTOR) pathway was inhibited by feed restriction, which was associated with decreased phosphor-mTOR, phosphorylated eukaryotic initiation factor 4E binding protein 1 (phosphor-4EBP1), and phosphorylated ribosomal protein S6 kinase (phosphor-S6K)."
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
"The activation of mTORC1 signaling causes enhanced protein translational machinery through the phosphorylation of ribosomal protein s6 kinase (S6K1) and the translational repressor eukaryotic initiation factor 4E‐binding protein 1 (4E‐BP1) (Fingar et al., xref ; Laplante & Sabatini, 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
"It localizes to the centrosomes, and takes part in the regulation of spindle pole organization and separation by phosphorylation of centrosomal Nek2-associated protein 1 (C-Nap1), rootletin, and ninein-like protein (Nlp). xref Nek2 has also been reported to act as a regulator of the spindle assembly checkpoint (SAC) through interaction or phosphorylation of highly expressed in cancer 1 (Hec1), mitotic arrest deficient-like 1 (Mad1), and mitotic arrest deficient-like 2 (Mad2). xref In recent publications, the role of Nek2 was probed by RNAi knockdown experiments and through inhibition by a covalent inhibitor."
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
"Secondly, phosphorylation of the eukaryotic initiation factor 4E binding protein 1 (4E-BP1) results in dissociation of 4E-BP1 from eukaryotic initiation of translation factor 4E (eIF4E), which is then able to enter the eIF4F complex to initiate cap-dependent translation [ xref ]."
sparser
"Reciprocally, a high level of SLC1A1 augments expression of activating transcription factor 4 (ATF4) and Cys/Glu antiporter xCT/SLC7A11 as well as phosphorylation of mTOR, the mTOR Substrate S6 Kinase 1 (S6K1), and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) [ 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
"Unlike its family members, no known ligand for HER2 has been identified, and signaling diversity is achieved by its dimerization partner.[ xref ] Dimerization leads to activation of the receptor TK domain, autophosphorylation, and ultimately activation of several downstream pathways, including the PI3K/Akt/mammalian target of rapamycin (mTOR) pathway and the Ras/Raf/mitogen-activated protein kinase (MAPK) pathway ( xref ).[ xref , xref ] Aberrant activation of the PI3K/Akt/mTOR pathway has been implicated in the development and progression of multiple malignancies.[ xref ] Subsequent activation of mTOR, a cytoplasmic serine/threonine kinase, results in the phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4EBP1) and p70S6 kinase (p70S6K), two regulators of protein synthesis."
sparser
"The levels of phosphorylated eukaryotic translation initiation factor 4E‑binding protein 1 (p‑4E/BP1) and phosphorylated ribosomal protein S6 kinase B1 (p‑S6K), and the expression of Runt‑related transcription factor 2 and Osterix, were concurrently quantified by western blot analysis."
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
"Inhibitors of the mTOR pathway, such as rapamycin and its analogs (ie, rapalogs), have been extensively studied as anticancer treatments, and several (temsirolimus, everolimus, and ridaforolimus) have been approved or are in phase 3 trials for different cancer types. xref , xref , xref However, these have yielded modest single‐agent clinical activity. xref , xref , xref Rapalogs predominantly inhibit mTOR complex 1 (mTORC1), and the efficacy of rapalogs may be partially restricted by failure to prevent AKT activation through mTOR complex 2 (mTORC2), a functionally distinct mTOR complex, or by limited inhibition of mTORC1‐mediated phosphorylation of eukaryotic translation initiation factor 4E–binding protein 1 (4EBP1). xref , xref The 4EBPs are critical mediators of mTORC1 effects on cell proliferation, xref and rapalogs do not inhibit mTORC1‐mediated phosphorylation of 4EBP1. xref Inhibition of both mTORC1 and mTORC2 leads to more effective inhibition of cancer cell proliferation than blocking mTORC1 alone. xref , xref Inhibitors of mTOR kinase that function through both the 4EBP1 and p70 S6 kinase 1 arms of mTORC1 and the mTORC2 kinase pathway are in clinical development. xref , xref "
sparser
"Furthermore, NK4 inhibited the activation of the RAC-α serine/threonine-protein kinase (Akt)/serine/threonine-protein kinase mTOR (mTOR) signaling pathway and reduced the levels of phosphorylated (p)-Akt, p-mTOR, ribosomal protein S6 kinase beta-1 and eukaryotic initiation factor 4E binding protein 1 in RPMI 8226 cells."
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
"For example, PKC-θ phosphorylates caspase recruitment domain–containing MAGUK protein 1 (Carma1), allowing this scaffolding protein to bind to signaling protein Bcl-10 and the IκB kinase IKKγ, promoting the assembly of the IKK signaling complex and coupling the TCR to the activation of the transcription factor NF-κB xref , xref ."
sparser
"In a previous study, we showed that ESCC was associated with the overexpression of Fascin, which was regulated by phosphorylated Specificity protein 1 (p-Sp1) via activation of the epidermal growth factor (EGF)/extracellular signal-regulated kinase (ERK) signaling pathway xref ."
sparser
"However, in study of Empagliflozin-ameliorated diabetic cardiac microvascular injury, activation of AMPK induces mitochondrial fission via dynamin-related/-like protein 1 (Drp1) phosphorylation and activation, which is a critical modulator to stimulate mitochondrial fission [ xref ]."
sparser
"HeLa cells represent an appropriate cell type to study Vpr-induced apoptosis, because ATR activation, breast cancer–associated protein 1 (BRCA1) phosphorylation, and GADD45α upregulation are conserved from HeLa cells to primary human CD4 + lymphocytes [ xref , xref , xref , xref ]."
sparser
"These activated sensors could increase the activity of the C-Jun amino-terminal kinase (JNK) and inhibitor of IκB (IKK-β), serine-phosphorylation of insulin-receptor substrate protein 1 (IRS-1), and the nuclear factor κB (NFκB) pathway, leading to the enhanced expression of pro-inflammatory cytokines [ xref , xref - xref ]."
sparser
"The structural abnormalities of the mitochondria are associated with reduced levels of phosphorylated (S637) dynamin related protein 1 (Drp1), a major mitochondrial fission-regulating protein, whereas mitochondrial fusion regulating proteins (OPA1 and MFN2) are relatively unaffected."
sparser
"Activation of mTORC1 increases ribosomal protein S6 kinase beta‐1 (p70S6K) and/or eukaryotic translation initiation factor 4E‐binding protein 1 (4E‐BP1) phosphorylation, which is the addition of phosphate to specific amino acid residue of protein kinase and activation with no effect on protein abundance (Bolster et al. xref ; Kubica et al. xref )."
sparser
"Activation of mTOR, as evident from phosphorylation of its downstream effector eukaryotic translation initiation factor 4E-binding protein 1, led to release of eukaryotic translation initiation factor 4E (eIF4E) which was subsequently phosphorylated by JNK leading to translation of pro-apoptotic proteins Bax and Bad without affecting the expression of anti-apoptotic protein Bcl-xl."
sparser
"Using both in vitro and in vivo models, we further demonstrate that BRD7 mediates phosphorylation of ribosomal protein S6 kinase (S6K) and leads to increased phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and therefore relieves its inhibition of the eukaryotic translation initiation factor 4E (eIF4E)."
sparser
"In terms of specific genes, the mRNA expression levels of TEA domain family proteins were significantly decreased in the combination group, whereas the phosphorylation of YY1 associated protein 1 and modulator of VRAC current 1 was significantly enhanced in the combination group."
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
"Thus, when conditions are favorable, mTORC1 triggers biosynthetic pathways essential for cell growth and proliferation, mainly through direct phosphorylation of ribosomal S6K and eukaryotic translation initiation factor 4E (eIF4E) binding protein 1 (4E-BP1) ( xref , xref , xref )."
sparser
"In contrast to SV40 sT and MCV LT, MCV sT exhibits oncogenic activity: it transforms rodent fibroblasts and promotes serum-independent growth of human fibroblasts. xref This is because MCV sT functions differently from SV40 sT; MCV sT promotes eukaryotic translation initiation factor 4E-binding protein 1 hyperphosphorylation and cap-dependent translation in a PP2A-independent manner, xref whereas SV40 sT induces dephosphorylation of 4E-binding protein 1 in a PP2A-dependent manner and inhibits cap-dependent translation. xref Moreover, MCV sT suppresses the activity of the E3 ubiqitin ligase SCF Fbw7 , which degrades MCV LT, and stabilizes MCV LT through its LT-stabilization domain; xref SV40 sT does not have an LT-stabilization domain."
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
"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
"Among others, ERK can activateresponse element-binding protein (CREB), a transcription factor [ xref ], promote phosphorylation of ribosomal protein S6 (rpS6) and hence translation [ xref ], as well as phosphorylate the eukaryotic translation initiation factor 4E (eIF4E) binding protein 1 (4EBP1), a repressor of translation, and release it from eIF4E [ xref ]."
sparser
"Therefore, we tested whether the effects of Prps2 translational control are mediated through eIF4E hyperactivation using specific inhibitors that target the activity of eIF4E. Specifically, we pretreated serum-starved fibroblasts with either an mTOR active site inhibitor (MLN0128) that blocks the phosphorylation of eIF4E binding protein 1 (4EBP1) as well as with a MEK1/2 inhibitor (PD901), which impairs eIF4E phosphorylation."
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
"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
"In addition, mDia1 interacts with cellular Src (c-Src), to guide its localization to the membrane, which subsequently results in Rac activation and membrane ruffle formation through the phosphorylation of breast cancer anti-estrogen resistance protein 1 (also known as p130Cas) [ xref , 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
"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
"Although the phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) was inhibited by TGF-β3 or IL-10 alone (Figures xref C,D; Figure S4D in Supplementary Material), the combination of TGF-β3 and IL-10 only inhibited phosphorylation of both 4E-BP and S6 kinase (S6K) (Figures xref C,D; Figure S4D in Supplementary Material)."
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
"However, 5C-feeding constantly increased tyrosine phosphorylation of insulin receptor substrate (IRS)-2 and threonine phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) in the liver during the examined periods, corresponding to the changes of their amounts."
sparser
"Compared with non-breeding pigeons, the expression of the phosphorylated IRS1 phosphorylated Akt, phosphorylated TOR, phosphorylated ribosomal protein S6 kinase, phosphorylated S6, phosphorylated eukaryotic initiation factor 4E binding protein 1 and eukaryotic initiation factor 4E were significantly up-regulated in the crop of pigeons in the lactation period."
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
"In kidney glomerular epithelial cells, high glucose (30 mM), but not equimolar mannitol, stimulated de novo protein synthesis and induced hypertrophy in association with increased phosphorylation of eukaryotic initiation factor 4E binding protein 1 and decreased phosphorylation of eukaryotic elongation factor 2, regulatory events in mRNA translation."
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
"Western blot analysis was used to measure the protein expression of phosphorylated mammalian target of rapamycin (p-mTOR), mTOR-mediated phosphorylated ribosomal protein S6 kinase beta-1 (p-S6K1), and phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p-4E-BP1) in the superficial dorsal horn of the spinal cord."
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 ."
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
"Activation of mTORC1 in mammalian cells results in the phosphorylation of Unc-51–like kinase/human autophagy-related protein 1 (ULK1/hAtg1), disrupting its interaction with adenosine monophosphate–activated protein kinase (AMPK) and inhibiting AMPK-mediated ULK1 activation ( xref )."
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
"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
"In in vitro-cultured ovaries, Rheb and GTP (is 100ngmL -1 Rheb and 500ngmL -1 GTP for 48h) significantly increased follicle diameter, the percentage of primary and secondary follicles and the umber of thecal cells, and upregulated expression of mTOR, phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), eukaryotic initiation factor (eIF) 4F and cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1)."
sparser
"Reelin is an extracellular protein, which affects several stages of neuronal migration and layering in the developing brain; reelin protein acts mainly by binding to low-density lipoprotein receptors and apolipoprotein E receptor 2, and then initiates the tyrosine phosphorylation of intracytoplasmic docking disabled protein 1 (Dab1) ( xref )."
sparser
"This observation allowed us to study some physiologically important regulatory mechanisms which were lost in GH cells as, for example, the inhibition of prolactin synthesis and release by dopamine: in normal anterior pituitary cells in culture, dopamine also prevented the thyrotropin-releasing hormone induced phosphorylation of protein 1."
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
"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
"Furthermore, most examined metabolic indices involved in muscle protein turnover and bone remodeling were unchanged, except for several indices in the inter-bout arousal group (IBA), i.e., increase in the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1) (IBA vs. SA, +80%) in the vastus medialis muscle, increase in chymotrypsin-like activity (IBA vs. SA, +62%) in the tibialis anterior muscle, increase in osteoblast number (IBA vs. SA, +110%; IBA vs. torpor (TOR), +68%) and osteoclast number (IBA vs. TOR, +105%) per bone surface in the tibia, and increase in osteoclast surface per bone surface (IBA vs. TOR, +128%) in the femur."
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
"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
"This second messenger molecule binds regulatory subunits of protein kinase A, whose catalytic subunits translocate into the nucleus where they phosphorylate the cAMP-responsive binding protein 1, which binds and activates synthetic P CRE promoters driving reporter gene expression ( xref )."
sparser
"Studies have revealed that rapamycin does not inhibit mTORC1 completely, leading to the concept that certain functions of mTORC1 are rapamycin-resistant (such as cap-dependent translation and the phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1; also known as 4EBP1)."
sparser
"It was hypothesized that there would be a coordinated regulation of eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1) phosphorylation by signalling cascades downstream of rises in intracellular [Ca(2+)] and decreased energy charge via AMP-activated protein kinase (AMPK) in contracting skeletal muscle."
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
"Insulin-, but not EGF-mediated VEGF protein expression was functionally connected to co-induced HMGR activity, as simvastatin restrictively interfered only with insulin-induced translation of VEGF mRNA by inhibition of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation."
sparser
"A recent study by Shuda and colleagues provided initial insight into the functional characteristics of MCPyV sT protein, which include physical association between sT and the PP2A A3 subunit in co-immunoprecipitation assays and promoting sustained phosphorylation of the cellular translation factor eIF4E binding protein 1 (4E-BP1) ( xref )."
sparser
"Several examples of interplay between O-GlcNAc and dephosphorylation have been reported, including the identification of a functional complex between OGT and protein phosphatase 1. xref For example, priming phosphorylation of folliculin-interacting protein 1 (FNIP1) at S938 by CK2 leads to many subsequent phosphorylation events of FNIP1, ultimately resulting in binding to Hsp90 to inhibit its ATPase activity."
sparser
"mTOR stimulates cell growth by activating ribosomal protein S6 kinase (S6K1) and by increasing phosphorylation of elongation factor-4E binding protein 1 (4E-BP1) resulting in protein synthesis. xref In addition, activated AMPK positively regulates 2 important proteins for the control of growth arrest and apoptosis, namely p53 and p21. xref In addition, c-Jun N-terminal kinase (JNK) and STAT3 are important downstream effectors of adiponectin."
sparser
"Although there is insufficient information about the action of LXA 4 on protein phosphorylation in various disease models, there is evidence that LXA 4 can block phosphorylation of leukocyte-specific protein 1 and alters phosphorylation and activation of components of the p38-MAPK cascade in chemoattractant-stimulated human neutrophils ( xref )."
sparser
"This translational regulation results from activation by TGF-beta 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
"MHY1485 treatment increased ribosomal protein S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation, which are downstream targets of mTOR complex 1 (mTORC1), but decreased phosphorylation of Akt on mTOR complex 2 (mTORC2) target site serine 473."
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
"mTOR signaling, through the phosphoinositide 3-kinase (PI3K)/Akt pathway, largely contributes to the regulation of cell survival, growth, and metabolism through phosphorylation of the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1 protein) and ribosomal protein S6 kinase ( xref )."
sparser
"Consequently, mutations within either Tsc1 or Tsc2 lead to increased levels of activated RHEB [ xref ], which causes hyperactivation of mammalian target of rapamycin (mTOR) signaling, a constitutive phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and activation of ribosomal protein S6 through S6K1 phosphorylation [ xref , xref ]."
sparser
"PI3K/Akt/mTOR is a major intracellular signaling pathway that regulates the proliferation, metabolism, motility, angiogenesis, and survival of normal cells and cancer cells. xref , xref – xref The PI3K heterodimer plays a central role in this pathway and is activated by a variety of receptor tyrosine kinases, including epidermal growth factor receptor, insulin-like growth factor 1 receptor (IGF1R), insulin receptor, and HER2. xref , xref – xref The activation of PI3K results in the downstream phosphorylation of Akt, a serine/threonine kinase, which in turn activates additional key downstream effectors, including mTOR. xref mTOR is a serine/threonine protein kinase that regulates cell proliferation, apoptosis, angiogenesis, and cellular metabolism through two multiprotein complexes: mTOR complex 1 (mTORC1), which is sensitive to rapamycin inhibition, and mTORC2. xref mTORC1 enhances mRNA translation and cell proliferation, growth, and survival through phosphorylation of the eukaryotic initiation factor 4E-binding protein 1 and the p70 ribosomal S6 kinase 1. xref , xref The function of mTORC2 is not as well understood but may be associated with cytoskeleton organization and cell proliferation, survival, and metabolism. 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
"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
"Detailed biochemical profiling of mammalian target of rapamycin signaling in tumors, skin, and peripheral blood mononuclear cells (PBMCs), after a single administration of 5 mg/kg RAD001, indicated that RAD001 treatment blocked phosphorylation of the translational repressor eukaryotic initiation factor 4E-binding protein 1 and inactivated the translational activator ribosomal protein S6 kinase 1 (S6K1)."
sparser
"LATS1/2, in turn, phosphorylate and inactivate Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1(WWTR1, also known as TAZ), which function as transcription co-activators and serve as Hippo pathway downstream effectors by regulating expression of genes involved in cell proliferation, death, and differentiation."
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)."
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
"Lapatinib (600nM) abolished the MAPK/ERK signaling as evidenced by reduction in ERK1/2 phosphorylation relative to control, and suppressed mTORC1 as illustrated by decreased phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and the ribosomal protein S6 kinases 1 and 2 (S6K1/2), as well as ribosomal protein S6 (rpS6) ( 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
"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 )."
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
"Besides the mammalian target of rapamycin (mTOR) kinase inhibitors or mammalian target of rapamycin complex 1 (mTORC1) inhibition in combination with the dual phosphatidylinositol 3 kinase (PI3K)/mTOR or AKT kinase inhibitors are more effective in inhibiting the phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and cap-dependent translation."
sparser
"mTOR (the mammalian target of rapamycin) is a crucial regulator of translation and together with associated proteins, raptor, GβL, PRAS40 and DEPTOR, phosphorylates the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), an inhibitor of cap-dependent translation, and the S6 kinase 1 which positively regulates different stages of protein synthesis [ xref ]."
sparser
"After stimulation with DAG, PKCθ undergoes conformational changes, and its activated form then phosphorylates caspase recruitment domain membrane-associated guanylate kinase protein 1 (CARMA1), leading to a conformational change that allows CARMA1 to associate with B-cell CLL/lymphoma 10 (Bcl-10) and mucosa-associated lymphoid tissue 1 (MALT1)."
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
"Several reports have shown that mTOR controls mRNA translation of eukaryotic cells by two mechanisms: (1) through phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), a protein that prevents translation when its non-phosphorylated form interacts with eIF4E (eukaryotic translation initiation factor 4E); and (2) through phosphorylation of RPS6 by RPS6 kinase (S6K1), which also promotes protein synthesis and cell proliferation [ xref , xref ] Previous studies showed that stimulation of mTORC1 by l -leucine boosted cell proliferation, protein synthesis, and development in zebrafish models of Roberts syndrome (RBS) in which mTOR signaling was strongly downregulated [ xref , xref ]."
sparser
"This was supported by decreased mRNA expression of insulin-like growth factor (IGF1), decreased activating phosphorylation of mammalian target of rapamycin (mTOR), decreased phosphorylation of 4E binding protein 1 (4E-BP1), and increased mRNA expression of key atrophy markers including: atrogin-1, forkhead box O3a (FOXO3a), myostatin ( MSTN ), and muscle-ring finger protein-1 (MuRF1)."
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
"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
"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
"Activation of BRAF signalling leads to increased phosphorylation of tumor necrosis factor receptor-associated protein 1 (TRAP1), which displays antiapoptotic properties in cancer cells. xref TRAP1 is also involved in the regulation of mPTP opening. xref To assess whether TRAP1 and mPTP opening play a role in BAY-induced cell death, we used a previously described method to measure mPTP opening. xref In brief, cells are stained with the fluorescent cation tetramethylrhodamine methyl ester (TMRM), which accumulates in the mitochondrial matrix in a Δ ψ -dependent manner. xref Next, reversible mPTP openings are photoinduced by controlled illumination of TMRM ( xref and 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
"Protein kinase C-θ (PKC-θ), a novel protein kinase C preferentially expressed in T lymphocytes, activates nuclear factor kappa B (NF-κB) through phosphorylation of CARD-containing MAGUK protein 1 (CARMA1) and assembly of the CARMA1–BCL10–MALT1 complex, participates in the differentiation of Th2 and Th17 cells [ xref ], localizes at the c-SMAC, and is involved in the translocation of the MTOC towards the IS where PKC-θ forms a ring-shaped area of signaling near the p-SMAC [ xref , xref ]."
sparser
"In mice, the mammalian target of rapamycin complex1 phosphorylates the translation repressor eukaryotic translation initiation factor 4E-binding protein 1 and regulates circadian clock entrainment and clock cell synchrony by promoting mRNA translation of Vip (vasoactive intestinal peptide) in the SCN ( xref )."
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
"In a recent paper, Djamei et al. (2007) showed that MAPK-mediated phosphorylation of VirE2-interacting protein 1 (VIP1) is required for its translocation into the host-cell nucleus and for activation of a pathogenesis-related gene, and that Agrobacterium uses the phosphorylated VIP1 to deliver its transfer-DNA molecule into the host cell."
sparser
"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
"This second messenger molecule binds regulatory subunits of protein kinase A (PKA), whose catalytic subunits translocate into the nucleus where they phosphorylate the cAMP-responsive binding protein 1 (CREB1) which binds and activates synthetic P CRE promoters driving reporter gene expression ( xref )."
sparser
"Upstream regulators, such as growth factors and amino acids, activate mTORC1, enhance protein synthesis through mTORC1-mediated phosphorylation of ribosomal protein S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which are the best described downstream effectors, and induce cell-cycle progression and growth24,27,28."
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
"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
"Immunohistochemical (IHC) analysis of Sox2-Lkb1 tumors demonstrated an absence of phosphorylated AMPK (pAMPK) and enhanced expression of phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p4EBP1), an mTOR substrate ( xref ; xref ), con-firming activation of the mTOR pathway ( 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
"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
"Taken together, the data suggest that the effect of rapamycin was not mediated by reduced phosphorylation of eukaryotic initiation factor 4E (eIF4E) binding protein 1 (BP1), because exercise did not cause a significant change in 4E-BP1(Thr-70) phosphorylation, 4E-BP1-eIF4E association, or eIF4F complex assembly concomitant with increased protein synthetic rates."
sparser
"These functions of NLRC3 were executed in a T-cell-intrinsic fashion: NLRC3 reduced K63-linked ubiquitination of TNF-receptor-associated factor 6 (TRAF6) to limit NF-κB activation, lowered phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and diminished glycolysis and oxidative phosphorylation."
sparser
"Although mTORC1 signaling impinges on a large array of cellular systems, it directly stimulates mRNA translation through activating phosphorylation of the ribosomal protein S6 kinase β-1 (RPS6KB1) and inhibitory phosphorylation of eIF4E binding protein 1 (EIF4EBP1) (ref. xref )."
sparser
"The abnormal activation of mTOR pathway has been demonstrated in many cancers [ xref – xref ]; the activated mTORC1 promotes the phosphorylation of p70S6K (p-p70S6K) and the releasing of phosphorylated eukaryotic elongation initiation factor 4E (eIF4E) binding protein 1 (4EBP1) from eIF4E, which ultimately result in enhanced translation of genes that are required for cell growth."
sparser
"In response to tick bites, the host skin promotes coagulation through high expression of fibrinogen and fibronectin, and vascular repair through high expression of integrin linked kinase and tenascin C, as well as accelerated phosphorylation of the phosphorylated protein Nck adaptor protein 1, and wound healing through high expression of ezrin and integrin."
sparser
"PPP1R3B is a relevant gene for the associated traits (glycemic and lipid metabolic disorders) since it encodes protein phosphatase 1 regulatory subunit 3B, which inhibits glycogen breakdown by regulating the interaction of phosphorylated protein 1 (PP1) with glycogen metabolism enzymes [ xref ]."
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
"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
"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
"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
"Both mTORC1 and mTORC2 additionally interact with DEPTOR, which inhibits their activities. xref Growth factors and nutrients, such as vitamins and amino acids, promote mTORC1 signaling through phosphorylation of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal S6 kinase 1 (S6K1), which are the best known downstream effectors of mTOR."
sparser
"Phosphorylation of the eukaryotic translation initiation factor 4E-binding protein 1, another downstream target of the mammalian target of rapamycin (mTOR), was stimulated to equivalent levels in S6K1(-/-) and S6K1(+/+) littermates during renal hypertrophy, indicating that mTOR was still activated in the S6K1(-/-) mice."