IndraLab
Statements
sparser
"Upon activation by receptor tyrosine kinases or G-protein coupled receptors, AKT activates mTOR, which in turn stimulates protein translation through inhibitory phosphorylation of eukaryotic translational initiation factor eIF4E-binding protein 1 (4E-BP1) that inhibits eIF4E, and activating phosphorylation of p70S6 kinase (S6K) that phosphorylates ribosomal S6 protein."
sparser
"Downstream of mTORC1, both S6K1 and S6K2 can phosphorylate S6, xref , xref although S6K1 has been shown to regulate muscle growth and insulin sensitivity independent of S6K2 activity. xref , xref In the present study, all genetic mouse groups showed increased phosphorylation and thus activity of S6K2 ( Figure xref )."
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"Upon activation, S6K1 phosphorylates ribosomal protein S6 (RPS6) to stimulate ribosomal biogenesis [XREF_BIBR], eukaryotic elongation factor 2 kinase (eEF2K) to de-repress translational elongation [XREF_BIBR], as well as eIF4B to heighten translational initiation [XREF_BIBR, XREF_BIBR]."
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"It is a serine/threonine kinase, which phosphorylates at least three downstream substrates : the translation repressor eIF4E binding protein (4E-BP) (von Manteuffel et al, 1997; Gingras et al, 1999; Nojima et al, 2003); p70S6K, which phosphorylates ribosome protein S6 (Nojima et al, 2003); and signal transducer and activator of transcription 3 (Stat3) (Yokogami et al, 2000; Kusaba et al, 2004)."
sparser
"In response to various stimuli, mTOR can be activated through phosphorylation, and the activated p-mTOR is involved in the regulation of protein synthesis by inducing the phosphorylation of p70S6K, which can phosphorylate the ribosomal protein S6 that is involved in protein translation ( xref , xref )."
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"The mTORC1 controls the rate of protein synthesis through phosphorylation and activation of its substrates, p70S6 ribosomal kinase 1 (p70S6K) and eukaryotic translation initiation factor 4E (eIF4E) binding protein-1 (4E-BP1) and once phosphorylated, p70S6K phosphorylates ribosomal protein S6 and 4E-BP1 becomes dissociated from eIF4 and promote mRNA translation and protein synthesis [XREF_BIBR]."
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"AA signaling is integrated by the mammalian target of rapamycin (mTOR), and mTOR is involved in the sensing of nutrient availability and modulation of insulin action in vivo via its further effects to activate S6 kinase 1 (S6K1), which phosphorylates the S6 ribosomal protein to enhance protein synthesis."
sparser
"Activation of mTOR leads to the phosphorylation of eukaryotic translation initiation factor eIF4E-binding protein 1 (4E-BP1) and p70S6K which phosphorylates S6. xref , xref xref show that pp70S6K-Thr-389/p70SK protein ratios were increased 1.8- and 3.1-fold in 1- and 10-day-old mutant hearts compared to wild-type, respectively."
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"mTOR allows eukaryotic cells to adjust their protein biosynthetic capacity XREF_BIBR, XREF_BIBR, XREF_BIBR through downstream effectors : (1) S6K1, a kinase that phosphorylates Rps6 and promotes protein synthesis and cell proliferation, and (2) eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), a protein that prevents translation when its unphosphorylated form interacts with eIF4E XREF_BIBR, XREF_BIBR, XREF_BIBR."
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"Both leucine and isoleucine have been shown to enhance the fractional protein synthesis rates in bovine mammary cells with the phosphorylation of mTOR and rpS6, or mTOR, S6K1, and rpS6 respectively [XREF_BIBR], while decreasing the abundance of proteasome protein, ubiquitinated protein, and the rate of protein degradation [XREF_BIBR]."
sparser
"Small interfering RNA knockdown of the mTOR substrate p70 S6 kinase abrogated PAK1 phosphorylation and enhanced HCV RNA abundance, whereas overexpression of a constitutively active alternate substrate, eukaryotic translation initiation factor 4E-binding protein 1, increased cap-independent viral translation and viral RNA abundance without influencing PAK1 phosphorylation."
sparser
"Whereas mTORC1-mediated phosphorylation of 4E-BP1 induces its dissociation from eIF4E, the rate-limiting factor for initiation of Cap-dependent translation ( xref ), phosphorylated S6K1 phosphorylates ribosomal protein S6, an essential regulator of protein translation and cell growth ( xref )."
sparser
"In response to mitogen stimulation, mTOR phosphorylates and activates S6K1, which in turn phosphorylates the 40S ribosomal protein S6, leading to the enhancement of translation of mRNAs with a 5′-terminal oligopyrimidine, including mRNAs that encode for ribosomal proteins and elongation factor-1."
sparser
"The mTORC1 controls the rate of protein synthesis through phosphorylation and activation of its substrates, p70S6 ribosomal kinase 1 (p70S6K) and eukaryotic translation initiation factor 4E (eIF4E) binding protein-1 (4E-BP1) and once phosphorylated, p70S6K phosphorylates ribosomal protein S6 and 4E-BP1 becomes dissociated from eIF4 and promote mRNA translation and protein synthesis [ xref ]."
sparser
"Anabolic pathways that promote fiber hypertrophy result in activation via phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR), which leads to phosphorylation and activation of p70 S6 kinase (p70S6K) that in turn phosphorylates the ribosomal protein S6 [ xref ]."
sparser
"Since phosphorylation of S6 ribosome protein (S6RP) by p70S6K can induce protein synthesis at the ribosome, the dramatic reduction of p70S6K after ATA treatment led to great reductions of new protein synthesis on several cell cycle-related proteins including cyclin D3, aurora kinase A, polo-like kinase, cyclin B1, survivin; and reduced the levels of EGFR and MET."
sparser
"Treatment of cells with the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] or rapamycin, an inhibitor of mammalian target of rapamycin and ribosomal p70 S6 kinase (p70S6K) phosphorylation, or with an adenovirus containing green fluorescent protein and a dominant-negative and kinase-dead Akt, effectively inhibited the insulin-mediated increase in alpha-class GST expression and GST activity toward NBD."
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"Although S6 ribosomal protein (S6) is phosphorylated by p70S6 kinase and therefore lies downstream of mTOR, previous studies have not found a correlation between S6 phosphorylation and either PTEN levels or PKB and Akt phosphorylation in primary GBM specimens [XREF_BIBR], likely reflecting the importance of other pathways in controlling mTOR activity in these tumors."
sparser
"Downstream substrates become phosphorylated including glycogen synthase kinase 3α and β (GSK3α/β, which are inhibited), and p70 ribosomal S6 kinases (p70S6K) which phosphorylate the small ribosomal subunit Rps6 to regulate translation of specific mRNAs, particularly increasing the protein synthetic machinery."
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"In LN229 and GAMG glioblastoma cells treated with either non targeting or PTEN targeting siRNA (siNT and siPTEN, respectively), both AD80 and LY-2779964 (LY64) were effective in reducing the S6K1 dependent phosphorylation of the ribosomal protein S6 (rpS6) at 3 hours (XREF_FIG, XREF_SUPPLEMENTARY)."
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"In LN229 and GAMG glioblastoma cells treated with either non targeting or PTEN targeting siRNA (siNT and siPTEN, respectively), both AD80 and LY-2779964 (LY64) were effective in reducing the S6K1 dependent phosphorylation of the ribosomal protein S6 (rpS6) at 3 hours (XREF_FIG, XREF_SUPPLEMENTARY)."
sparser
"MTOR phosphorylates a series of growth- and metabolism-associated substrates, among which the best-characterized target is ribosomal protein S6 (RPS6) kinase 1 (S6K1). xref MTOR phosphorylates S6K1 at Thr389, and activated S6K1 further phosphorylates RPS6 to regulate protein translation, synthesis, and metabolism. xref To investigate the role of MET in MTOR activation, we used WT and Met -KO HepG2 cells and observed that the amino acid-enhanced phosphorylation of S6K1 at Thr389 was repressed in MET-KO cells (Fig. xref )."
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"The S6K1 gene can promote protein translation by stimulating the phosphorylation of downstream eIF-4B, RPS6, eIF-2, and PAPB [40], and the SLC3A2, IRS1, PDK, P13K, TSC1, TSC2, mTORC1, eIF4EBP1, S6K1, and eIF4B genes are related to nitrogen metabolism in the liver; moreover, these genes would become overexpressed when blood ammonia increased to increase urea synthesis and balance the blood ammonia [41]."
sparser
"RPS6KB1 is ribosomal protein S6 kinase B1, and its upstream is the key protein mTOR, which activates RPS6KB1 through phosphorylated mTOR and then activated RPS6KB1 phosphorylates its downstream molecules RPS6 and EIF4B, thereby controlling the downstream process of protein synthesis during cell growth ( xref ; xref )."
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"mTORC1 controls mRNA translation via at least two well-established downstream targets: p70S6 kinase (p70S6K), which phosphorylates several translation factors including the ribosomal protein S6 (pS6), and repressor proteins of eukaryotic initiation factor 4E (eIF4E) termed 4E-BPs [5]."
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"mTORC1 controls mRNA translation via at least two well-established downstream targets: p70S6 kinase (p70S6K), which phosphorylates several translation factors including the ribosomal protein S6 (pS6), and repressor proteins of eukaryotic initiation factor 4E (eIF4E) termed 4E-BPs [5]."
sparser
"The p70S6K
protein phosphorylates the 40S ribosomal protein S6 and the translation initiation
factor eIF4B. The pivotal role of mTOR pathway in the generation of cardiac
hypertrophy is underscored by the studies which show that rapamycin, an inhibitor
for mTOR, attenuates the development of cardiac hypertrophy induced by aortic
constriction. xref Our data
show that the mTOR pathway is upregulated in the hypertrophic heart, which is
attenuated in the cathepsin K knockout mice."
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"In response to numerous intracellular and extracellular stimuli, mTORC1 phosphorylates eukaryotic initiation factor 4E binding protein-1 (4E-BP1) and S6 kinase 1 (S6K1), which exerts an essential role in increasing translation of a subset of mRNAs and accelerating growth and proliferation XREF_BIBR XREF_BIBR."
sparser
"P70S6, a serine/threonine kinase, is a downstream signal of the PI3K/Akt/mammalian target of rapamycin and mitogen-activated protein kinase cascades. xref On activation, p70S6 subsequently phosphorylates ribosomal protein S6, which, in turn, promotes protein translation and cell growth. xref In addition, we also found that boehmenan remarkably inhibited the expression of p-Akt, p-70S6, and p-S6, which is critical for cell survival and resistant to apoptosis. xref Thus, suppression of STAT3 and PI3K/Akt pathway contributed to cell apoptosis and inhibition of cell survival triggered by boehmenan."
sparser
"S6K1 and S6K2 phosphorylate and activate the 40S ribosomal protein
S6, which promotes protein synthesis through an increased rate of
mRNA transcription. xref S6K1 also regulates
cell size and progression through the cell cycle, xref − xref in addition
to promoting cell survival by inactivating the proapoptotic protein
BAD. xref "
sparser
"Its major effects are mediated by phosphorylation of proteins involved in the regulation of protein synthesis such as 4EBP1 and p70S6K, with subsequent phosphorylation of ribosomal S6 protein by p70S6K, and the components of ULK1 kinase that play a critical role in the regulation of autophagy [ xref ]."
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"In order to evaluate the possible targeting of the mTOR pathway by both MTH (through raptor) and RAPA (through mTOR binding by FKBP12), we compared the effects of these two inducers on the phosphorylation of p70S6Kinase (p70S6K), which specifically phosphorylates the ribosomal protein S6, strongly involved in sustaining protein synthesis and cell growth [XREF_BIBR, XREF_BIBR]."
sparser
"This is done through activation of ribosomal S6 kinase 1 (S6K1) and inhibition of eukaryotic initiation factor 4E binding protein 1 (4E-BP1) by phosphorylation.[16] The resulting activated S6K1 can phosphorylate ribosomal protein S6.[17] Generally, phosphorylation of S6 is a good indicator of S6K1 activity."
sparser
"Although animal data presented by Nakajima et al. ( xref ) also observed no changes in metabolic stress after repeated bouts of REST + BFR versus REST (quantified as AMPK phosphorylation), they did observe greater p70S6K and ribosomal S6 phosphorylation in skeletal muscle tissue."
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"In mammals, upon stimulation by growth factors including insulin, the mammalian TOR (mTOR) cooperates with PI3K dependent effectors to activate p70 ribosomal protein S6 kinase 1 (S6K1), thereby phosphorylating the 40S-ribosomal protein S6, and subsequently enhances translation of the 5 '-terminal oligopyrimidine (5 '-TOP) sequences that encode components of the translational machinery."
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"Another well established target of the TORC1 complex is the S6 protein kinase S6K1, which phosphorylates ribosomal protein S6, an event that controls elongation factor 2 kinase, but probably not translation of mRNAs with a 5 '-oligopyrimidine tract as originally suggested [XREF_BIBR - XREF_BIBR]."
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"At a downstream level, mTORC1 activates p70 ribosomal protein S6 kinase1 (p70S6K), which further phosphorylates ribosomal protein S6 (RPS6) and carbamoyl phosphate synthetase 2-aspartate transcarbamoylase-dihydroorotase (CAD), responsible for inducing ribosome biogenesis and de novo pyrimidine biosynthesis, respectively [58]."
sparser
"Although the signaling pathways controlling translation of TOP mRNAs are still under intensive investigations, it seems that RPS6 phosphorylation by S6Ks, mTOR activity, and the PI3-kinase pathway activation in response to growth or mitotic signals is essential for the translational regulation of TOP mRNAs (for review [ xref , xref ])."
sparser
"The p70-S6K1 protein is activated by mTOR and subsequently phosphorylates the ribosomal S6 protein (RPS6), eukaryotic transcription initiation factor 4B (EIF4B), and eukaryotic elongation factor 2-kinase (eEF2 k) and is a positive regulator of protein translation (reviewed in [ xref ])."
sparser
"The p70-S6K1 protein is activated by mTOR and subsequently phosphorylates the ribosomal S6 protein (RPS6), eukaryotic transcription initiation factor 4B (EIF4B), and eukaryotic elongation factor 2-kinase (eEF2 k) and is a positive regulator of protein translation (reviewed in [ xref ])."
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"Based on our data pointing to critical involvement of mTOR signaling in TTL short / high-risk leukemia, we addressed mTOR pathway activity by investigating phosphorylation of key signaling molecules : ribosomal protein S6 (S6), a downstream molecule which is phosphorylated by the ribosomal protein S6 kinase (p70S6K1) upon mTOR activation; and AKT, an upstream signaling kinase that is activated by phosphatidylinositol 3-kinase (PI3K) also mediating mTOR activation."
sparser
"While p70S6K phosphorylates ribosomal S6 protein potentially modulating its activity, 4EBP1 binds and inactivates a factor of initiation of Cap-dependent transcription eIF4E. In its hypophosphorylated forms, 4EBP1 has high avidity to eIF4E causing inhibition of translation of many mRNA with structured 5′UTR, encoding proteins critical for cell growth and metabolism."
sparser
"Binding of insulin to its receptor triggers activation of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway and subsequent activation of mTOR; activation of mTOR results in the phosphorylation and activation of S6K1 and 4EBP1, which in turn phosphorylates ribosomal protein S6 and, finally, stimulates protein synthesis [ xref , xref ]."
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"Although single knockout or knockdown of S6K1 or S6K2 was insufficient to entirely reduce rpS6 phosphorylation, the combination of S6K1 and S6K2 inactivation cooperated to substantially reduce rpS6 phosphorylation, consistent with overlapping and compensatory functions in GBM (Fig. 4A–C)."
sparser
"It is a serine/threonine kinase, which phosphorylates at least three downstream substrates: the translation repressor eIF4E-binding protein (4E-BP) ( xref ; xref ; xref ); p70S6K, which phosphorylates ribosome protein S6 ( xref ); and signal transducer and activator of transcription 3 (Stat3) ( xref ; xref )."
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"To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS) related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K), an extensively studied effector of mTOR Complex 1 (mTORC1) and the phosphorylated phosphatase and tensin homolog (pPTEN), a negative regulator of mTORC1 pathway."
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"Based on our data pointing to critical involvement of mTOR signaling in TTL short / high-risk leukemia, we addressed mTOR pathway activity by investigating phosphorylation of key signaling molecules : ribosomal protein S6 (S6), a downstream molecule which is phosphorylated by the ribosomal protein S6 kinase (p70S6K1) upon mTOR activation; and AKT, an upstream signaling kinase that is activated by phosphatidylinositol 3-kinase (PI3K) also mediating mTOR activation."
reach
"In response to various stimuli, mTOR can be activated through phosphorylation, and the activated p-mTOR is involved in the regulation of protein synthesis by inducing the phosphorylation of p70S6K, which can phosphorylate the ribosomal protein S6 that is involved in protein translation."
sparser
"S6 phosphorylation by S6K1 is involved in a plethora of biologic processes including cell proliferation, translation initiation, and metabolic regulation and is known to be activated downstream of the PI3K-mTOR axis ( xref – xref ); very little has been studied regarding the specific involvement of S6K1 in drug resistance."