Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P23443 and P42345	Pubmed	SVM Score :1.2098753
Coimmunoprecipitation analysis demonstrates that mTOR physically associates with S6K1 upon FGF 9 treatment , whereas ablation of mTOR activity using RNA interference or pharmacological inhibitor blocks S6K1 phosphorylation and cell proliferation induced by FGF 9 . 1.2098753^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
BACKGROUND : The mammalian target of rapamycin ( mTOR ) belongs to the family of phosphoinositide ( PI ) kinase related kinases that includes the ataxia telangiectasia gene product ( ATM ) . mTOR plays a critical role in controlling translational effectors such as p 70 S6 kinase alpha ( p 70 alpha ) and eukaryotic initiation factor 4E binding protein 1 ( 4EBP1 ) . ^^^ Deletion of the C terminal residues did not adversely affect the expression of mTOR , but caused a nearly complete loss of the mTOR protein kinase activity toward both 4EBP1 and p 70 alpha in vitro . ^^^ These deletions also abolished the ability of a rapamycin resistant mTOR mutant to rescue the activity of p 70 alpha from inhibition induced by rapamycin in vivo . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mammalian target of rapamycin ( mTOR ) controls cell growth in response to amino acids and growth factors , in part by regulating p 70 S6 kinase alpha ( p 70 alpha ) and eukaryotic initiation factor 4E binding protein 1 ( 4EBP1 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Using FRAP variants that do not bind FKBP 12 rapamycin , we demonstrate here that FRAP is a rapamycin sensitive regulator of p70S6k in vivo and that the kinase activity of FRAP is required for this regulation . ^^^ Deletion studies indicate that the kinase activity of FRAP alone is not sufficient for control of p70S6k and that an amino terminal domain in FRAP is also required . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Instead , this complex physically interacts with a novel protein , designated `` mammalian target of rapamycin ' ' ( mTOR ) , which has sequence homology with the catalytic domain of phosphatidylinositol kinases and may therefore be itself a kinase . mTOR may act upstream of ( p70s6K ) and cdk 2 cyclin E in a linear or bifurcated pathway of growth regulation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Exogenous insulin like growth factor ( IGF ) 1 protected both Rh 1 and Rh 30 from apoptosis , without reactivating ribosomal p 70 S6 kinase ( p70S6K ) downstream of mTOR . ^^^ To examine the rate at which the mTOR pathway recovered , the ability of IGF 1 to stimulate p70S6K activity was followed in cells treated for 1 h with rapamycin and then allowed to recover in medium containing > or =100 fold excess of FK 506 ( to prevent rapamycin from rebinding to its cytosolic receptor FKBP 12 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Regulation of cell growth and cyclin D 1 expression by the constitutively active FRAP p70s6K pathway in human pancreatic cancer cells . ^^^ The FRAP p70s6K signaling pathway was found to be constitutively phosphorylated / active in MiaPaCa 2 and Panc 1 human pancreatic cancer cells and a pancreatic cancer tissue sample as judged by the retarded electrophoretic mobility of the two major FRAP downstream targets , p70s6K and 4E BP 1 . ^^^ Treatment of cells with rapamycin , a selective FRAP Inhibitor , inhibited basal p70s6K kinase activity and induced dephosphorylation of p70s6K and 4E BP 1 . ^^^ Thus , inhibitors of the constitutively active FRAP p70s6K pathway may provide a novel therapeutic approach for pancreatic cancer . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The activation of p 70 S6k is mediated by a signaling pathway involving the mammalian target of rapamycin ( mTOR ) , which also modulates other translation factors . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Transient transfection assays with mTOR mutants bearing Ala substitutions at Ser 2448 and / or Thr 2446 indicated that AKT dependent mTOR phosphorylation was not essential for either PHAS 1 phosphorylation or p70S6K activation in HEK cells . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapamycin , a specific inhibitor of the mammalian target of rapamycin ( mTOR ) , which is an upstream signaling of p70S6K , completely inhibited FCS induced cell size increases and protein synthesis , but had no effect on SKA mRNA expression . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapamycin kills normal cells more readily in normal than in A T cells , and inhibits the FRAP target p 70 S6 kinase ( p70S6K ) more readily in normal than in A T cells . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The PI3K ( phosphatidylinositol 3 kinase ) mTOR ( mammalian target of rapamycin ) pathway is important for regulation of acinar cell protein synthesis because it leads to both activation of p70S6K and regulation of the availability of eIF4E in response to CCK . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Recent findings have demonstrated that the branched chain amino acid leucine can activate the translational regulators , phosphorylated heat and acid stable protein regulated by insulin ( PHAS 1 ) and p 70 S6 kinase ( p70S6k ) , in an insulin independent and rapamycin sensitive manner through mammalian target of rapamycin ( mTOR ) , although the mechanism for this activation is undefined . ^^^ These findings indicate that leucine at physiological concentrations stimulates p70s6k phosphorylation via the mTOR pathway , in part , by serving both as a mitochondrial fuel and an allosteric activator of GDH . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
FRAP p70s6K signaling is required for pancreatic cancer cell proliferation . ^^^ BACKGROUND : FRAP p70s6K signaling regulates mitogenic responses to growth factors in eukaryotic cells . ^^^ CONCLUSIONS : FRAP p70s6K signaling appears to be necessary for G ( 1 ) to S phase progression and proliferation in pancreatic cancer cells . ^^^ This supports earlier work demonstrating a similar regulatory role for PI 3 ' kinase , an upstream activator of FRAP p70s6K . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Blocking mTOR affects the activity of the 40S ribosomal protein S 6 kinase ( p70s6k ) and the function of the eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) , leading to growth arrest in the the G 1 phase of the cell cycle . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In contrast with the situation for 4E BP 1 , glucose does not allow full activation of the 70 kDa ribosomal protein S 6 kinase ( p 70 S6k ; another target of mTOR signalling ) or phosphorylation , in vivo , of its substrate , ribosomal protein S 6 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mechanism by which PI3K and FRAP cooperate to induce p70S6K activation remains unclear . ^^^ Here we show that the p 85 regulatory subunit of PI3K also controls p70S6K activation by mediating formation of a ternary complex with p70S6K and FRAP . ^^^ The p 85 C terminal SH 2 domain is responsible for p 85 coupling to p70S6K and FRAP , because deletion of the C terminal SH 2 domain inhibits complex formation and impairs p70S6K activation by PI3K . ^^^ Formation of this complex is not required for activation of a FRAP independent form of p70S6K , however , underscoring the role of p 85 in regulating FRAP dependent p70S6K activation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We conclude that the activation of the Akt / mTOR pathway and its downstream targets , p70S6K and PHAS 1 / 4E BP 1 , is requisitely involved in regulating skeletal muscle fibre size , and that activation of the Akt / mTOR pathway can oppose muscle atrophy induced by disuse . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Pretreatment of cells with wortmannin and LY 294002 , inhibitors of PI3K , or rapamycin , an inhibitor of the mammalian target of rapamycin kinase and p70S6K , diminished the ANG 4 mediated activation of PDK 1 and PKB alpha as well as phosphorylation of p70S6K . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here we demonstrate that primary tumors from tuberous sclerosis complex ( TSC ) patients and the Eker rat model of TSC expressed elevated levels of phosphorylated mammalian target of rapamycin ( mTOR ) and its effectors : p70S6K , S 6 ribosomal protein , 4E BP 1 , and eIF4G . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Paclitaxel induced p70S6K ( T421 / S424 ) phosphorylation requires both de novo RNA and protein synthesis via multiple signaling pathways including ERK1 / 2 MAP kinase , JNK , PKC , Ca ( ++ ) , PI3K , and mammalian target of rapamycin ( mTOR ) . ^^^ Inhibitors of mTOR , PI3K , and Ca ( ++ ) impair p70S6K activity , whereas inhibitors of JNK and PKC stimulate p70S6K activity . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The insensitivity of the rapamycin resistant p 70 S6k variant to AICAR treatment suggests that the inhibition of p 70 S6k is mediated through a common effector , supporting a model whereby mTOR and its downstream effector are controlled by AMPK . ^^^ In addition to the mTOR signal acting as a priming switch that modulates p 70 S6k activation , AMPK appears to provide an overriding switch linking p 70 S6k regulation to cellular energy metabolism . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mammalian target of rapamycin ( mTOR ) controls multiple cellular functions in response to amino acids and growth factors , in part by regulating the phosphorylation of p 70 S6 kinase ( p70S6k ) and eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) . ^^^ Raptor ( regulatory associated protein of mTOR ) is a recently identified mTOR binding partner that also binds p70S6k and 4E BP 1 and is essential for TOR signaling in vivo . ^^^ Herein we demonstrate that raptor binds to p70S6k and 4E BP 1 through their respective TOS ( conserved TOR signaling ) motifs to be required for amino acid and mTOR dependent regulation of these mTOR substrates in vivo . ^^^ A point mutation of the TOS motif also eliminates all in vitro mTOR catalyzed 4E BP 1 phosphorylation and abolishes the raptor dependent component of mTOR catalyzed p70S6k phosphorylation in vitro . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The immunosuppressant FK 506 failed to inhibit p70S6K activation , but was able to rescue the rapamycin induced downshift , pointing to a role for the mammalian target of rapamycin ( mTOR ) kinase . ^^^ Thus , GM CSF causes the dual activation of a rapamycin resistant , MAPK related kinase , that targets Thr421 / Ser424 S6K phosphorylation , and a rapamycin sensitive , mTOR related kinase , that targets Thr 389 , both of which are needed in cooperation to achieve full activation of neutrophil p70S6K . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We show here that hypoxia rapidly and reversibly triggers hypophosphorylation of mTOR and its effectors 4E BP 1 , p70S6K , rpS 6 , and eukaryotic initiation factor 4G . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Because mTOR activates both the 40S ribosomal protein S 6 kinase ( p70s6k ) and the eukaryotic initiation factor 4E binding protein 1 , rapamycin like compounds block the actions of these downstream signaling elements , which results in cell cycle arrest in the G 1 phase . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapamycin , a specific inhibitor of p70S6K activation by the mammalian target of rapamycin , completely prevents GDNF induced proliferation and activation of p70S6K . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapamycin , an inhibitor of the mammalian target of rapamycin ( mTOR ) , did not mimic the effect of oxygen deprivation to inhibit protein synthesis in cardiomyocytes or lead to eEF 2 phosphorylation in perfused hearts , suggesting that AMPK activation did not inhibit mTOR / p70 ribosomal protein S 6 kinase ( p70S6K ) signaling . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We demonstrate that leukocyte chemotaxis is prevented by the macrolide immunosuppressant rapamycin , a specific inhibitor of the mammalian target of rapamycin ( mTOR ) / ribosomal p 70 S6 kinase ( p70S6K ) pathway . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Treatment with rapamycin inhibited EGF induced phosphorylation and activation of ribosomal p 70 S6 protein kinase ( p 70 S6K ) , an mTOR downstream target , but had no effect on phosphorylation and activation of Akt . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapamycin , an inhibitor of mammalian target of rapamycin , did not block the insulin mediated rescue from macroautophagy , although it nullified the activation of p70S6K and cell growth . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
At a molecular level , this dual control of p 70 S6K activity is attributable to phosphorylation of the two p 70 S6K sites : The Ptd Ins 3 , 4 , 5P3 dependent kinasel ( PDK 1 ) phosphorylates p 70 S6K at a Thr on the activation loop , whereas mTOR phosphorylates a Thr located in a hydrophobic motif carboxyterminal to the catalytic domain . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Modulation of the protein kinase activity of mTOR . mTOR is a founding member of a family of protein kinases having catalytic domains homologous to those in phosphatidylinositol 3 OH kinase . mTOR participates in the control by insulin of the phosphorylation of lipin , which is required for adipocyte differentiation , and the two translational regulators , p70S6K and PHAS 1 . ^^^ In contrast , rapamycin FKBP 12 inhibited mTOR activity towards both PHAS 1 and p70S6K , although this complex inhibited the phosphorylation of some sites more than that of others . ^^^ Unexpectedly , this mutation markedly decreased the ability of mTOR to phosphorylate certain sites in both PHAS 1 and p70S6K . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Unexpectedly , p70S6K and 4EBP1 , downstream components of mTOR , were activated in atrophic rat heart . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Time restricted role for dendritic activation of the mTOR p70S6K pathway in the induction of late phase long term potentiation in the CA 1 . ^^^ Second , we observed that Thr 389 phosphorylated p 70 S6 kinase ( p70S6K ) , the main active phosphoform of the mTOR effector p70S6K , was induced in an N methyl D aspartate and phosphatidylinositol 3 kinase dependent manner throughout the dendrites but not in the cell bodies of CA 1 neurons in hippocampal slices after L LTP induction . ^^^ Taken together , the present data suggest that the N methyl d aspartate , phosphatidylinositol 3 kinase dependent dendritic activation of the mTOR p70S6K pathway is necessary for the induction phase of protein synthesis dependent synaptic plasticity . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Insulin treatment induced p70S6K , mTOR , and Akt phosphorylation , effects that were completely prevented by the PI3K inhibitor , LY 294002 . ^^^ Insulin induced phosphorylation of p70S6K and mTOR was prevented by the mTOR inhibitor , rapamycin . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Mammalian target of rapamycin ( mTOR ) is a PKB substrate , and regulates p 70 S6 kinase ( p 70 S6K ) . ^^^ Mammalian target of rapamycin ( mTOR ) is a PKB substrate , and regulates p 70 S6 kinase ( p 70 S6K ) . ^^^ DESIGN : We measured the effect of rapamycin , a specific inhibitor of mTOR , on insulin induced 3T3 L 1 adipogenesis and on insulin stimulated p 70 S6K activation . ^^^ CONCLUSION : Our data suggest that adipogenic mTOR signaling occurs via the 4E BP1 / eIF4E pathway , rather than through p 70 S6K . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Recent studies revealed a role of tuberin , a TSC 2 product , in suppressing the p 70 S6 kinase ( p70S6K ) activity via inhibition of mammalian target of rapamycin ( mTOR ) . ^^^ Phosphorylated S 6 protein , a substrate of p70S6K , was expressed in the early lesions in Eker rats , and this expression was suppressed by the treatment of rapamycin , an inhibitor of mTOR . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Unique , highly proliferative growth phenotype expressed by embryonic and neointimal smooth muscle cells is driven by constitutive Akt , mTOR , and p70S6K signaling and is actively repressed by PTEN . ^^^ Western blot analysis demonstrated that cultured embryonic and neointimal SMCs that exhibited serum independent growth capabilities expressed high levels of S6RP and constitutively active Akt , mTOR , and p70S6K . ^^^ Growth of SMCs that exhibit this phenotype is dependent on constitutive Akt and mTOR / p70S6K signaling and is actively inhibited through the timed acquisition of the endogenously produced growth suppressor PTEN . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The activity of p 70 S6K and phosphorylation of the S 6 protein was completely blocked by rapamycin and significantly decreased upon treatment of the cells with wortmannin , indicating an involvement of the PI 3K pathway in concert with the signalling pathway of mTOR in IL 2 dependent phos phorylation of ribosomal protein S 6 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Contraction mediated mTOR , p70S6k , and ERK1 / 2 phosphorylation in aged skeletal muscle . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Phophatidylinositol 3 kinase / mammalian target of rapamycin / p70S6K regulates contractile protein accumulation in airway myocyte differentiation . ^^^ Skeletal and vascular smooth muscle hypertrophy is induced by phosphatidylinositide 3 kinase ( PI ( 3 ) kinase ) via mammalian target of rapamycin ( mTOR ) and p70S6 kinase ( p70S6K ) . ^^^ Immunocytochemistry revealed that activation of PI3K / mTOR / p70S6K occurred almost exclusively in myocytes that acquire the contractile phenotype . ^^^ Inhibition of PI ( 3 ) kinase or mTOR with LY 294002 or rapamycin blocked p70S6K activation , prevented formation of large elongated contractile phenotype myocytes , and blocked accumulation of SM 22 and smMHC . ^^^ These studies provide primary evidence that PI ( 3 ) kinase and mTOR activate p70S6K in airway myocytes leading to the accumulation of contractile apparatus proteins , differentiation , and growth of large , elongated contractile phenotype airway smooth muscle cells . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The phosphatidylinositol 3 kinase ( PI3K ) inhibitors , wortmannin and LY 294002 [ 2 ( 4 morpholinyl ) 9 phenyl 4H 1 benzopyran 4 one ] , dominant negative Akt , or rapamycin , an inhibitor of mTOR ( mammalian target of rapamycin ) and ribosomal p 70 S6 kinase ( p70S6K ) phosphorylation , inhibited the insulin mediated increase in GCLC protein and GSH levels . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In response to IGF 1 , Akt activates downstream effectors , mTOR and p70S6K to stimulate protein synthesis thereby increasing the cytoplasmic compartment in muscle fibers . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In addition , there was a concentration dependent inhibition of cell migration and p70S6K phosphorylation ( Thr ( 389 ) and Thr ( 421 ) / Ser ( 424 ) ) in the presence of Rapamycin , a specific inhibitor of the mammalian target of rapamycin ( mTOR , a downstream of AKT ) . ^^^ Taken together , our data suggest that EGF induced trophoblast migration involves the coordinated regulation of both PI3K / AKT and MAPK signalling pathways . mTOR / p70S6K is important in PI3K but not MAPK mediated trophoblast migration in response to EGF . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Furthermore , rapamycin , an inhibitor of mTOR and consequently of p70S6K , did not alter PRL stimulation of c Myc and c Fos mRNA expression and it had a very minor inhibitory effect on PRL stimulation of W 53 cell proliferation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In addition , AICAR inhibited two key enzymes involved in protein synthesis , mTOR and p70S6K , and blocked the ability of the androgen R 1881 to increase cell growth and the expression of two enzymes for de novo fatty acid synthesis , acetyl CoA carboxylase and fatty acid synthase , in the LNCaP cells . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mTOR / p70S6K signal transduction pathway plays a role in cardiac hypertrophy and influences expression of myosin heavy chain genes in vivo . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Because mTOR activates both the 40S ribosomal protein S 6 kinase ( p70s6k ) and the eukaryotic initiation factor 4E binding protein 1 , its inhibitors cause G 1 phase cell cycle arrest . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Thyroid hormone induces rapid activation of Akt / protein kinase B mammalian target of rapamycin p70S6K cascade through phosphatidylinositol 3 kinase in human fibroblasts . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
HCMV infection does not induce mTOR independent phosphorylation of a third mTOR effector , p70S6 kinase ( p70S6K ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mTOR kinase controls the translation machinery , in response to amino acids and growth factors , via activation of p 70 ribosomal S 6 kinase ( p70S6K ) and inhibition of eIF 4E binding protein ( 4E BP 1 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Using pharmacological inhibitors , we established that PI3K Akt , mTOR p 70 ribosomal protein S 6 kinase ( p70S6K ) , and EKR1 / 2 signaling pathways play a critical role in hypoxia induced adventitial fibroblast proliferation . ^^^ We found that hypoxia induced significant increases in mTOR , p70S6K , 4E BP 1 , and S 6 ribosomal protein phosphorylation , as well as dramatic increases in p70S6K activity . ^^^ The activation of p70S6K / S6 pathway was sensitive to inhibition by rapamycin and LY 294002 , indicating that mTOR and PI3K / Akt are upstream signaling regulators . ^^^ Thus our data demonstrate that hypoxia induced adventitial fibroblast proliferation requires activation and interaction of PI3K , Akt , mTOR , p70S6K , and ERK1 / 2 and provide evidence for hypoxic regulation of protein translational pathways in cells exhibiting the capability to proliferate under hypoxic conditions . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Investigation of proteins in the phosphatidylinositol 3 ' kinase / Akt signaling pathway in PTEN delivered mouse lung revealed that the PTEN protein was highly expressed , whereas the protein levels of PDK 1 , total Akt 1 , phospho ( Thr 308 ) Akt , phospho ( Ser 2448 ) mTOR , p70S6K , and 4E BP 1 were decreased to varying degrees . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
By using both pharmacologic and genetic approaches , we found that in addition to ERK1 / 2 , phosphatidylinositol 3 kinase ( PI3K ) , Akt , mammalian target of rapamycin ( mTOR ) , and p 70 S6K dependent signaling pathways are required for ATP induced proliferation of adventitial fibroblasts . ^^^ Extracellular ATP induced dramatic increases in mTOR and p 70 S6K phosphorylation . ^^^ This activation of the mTOR / p70 S 6 kinase ( p 70 S6K ) pathway in response to ATP is because of independent contributions of PI3K / Akt and ERK1 / 2 pathways , which converge on the level of p 70 S6K . ^^^ ATP dependent activation of mTOR and p 70 S6K also requires additional signaling inputs perhaps from pathways operating through Galpha or Gbetagamma subunits . ^^^ Collectively , our data demonstrate that ATP induced adventitial fibroblast proliferation requires activation and interaction of multiple signaling pathways such as PI3K , Akt , mTOR , p 70 S6K , and ERK1 / 2 and provide evidence for purinergic regulation of the protein translational pathways related to cell proliferation . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Accordingly , 2 downstream effectors of mTOR , 4E BP 1 and p70S6K , are phosphorylated in a rapamycin sensitive manner in a series of 23 AML cases . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We found that overexpression of the DGKzeta , but not of the alpha isoform , in serum deprived HEK 293 cells induced mTOR dependent phosphorylation of p70S6 kinase ( p70S6K ) . ^^^ The effect of this DGK isoform on p70S6K hyperphosphorylation required the mTOR PA binding region . ^^^ Down regulation of endogenous DGKzeta by small interfering RNA in HEK 293 cells diminished serum induced p70S6K phosphorylation , highlighting the role of this isoform in the mTOR pathway . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
IRS 1 / 2 serine phosphorylation , IR / protein tyrosine phosphatase 1B ( PTP1B ) association , and mammalian target of rapamycin ( mTOR ) / p70 ribosomal S 6 kinase ( p 70 S6K ) activity were also evaluated in the liver , skeletal muscle and white adipose tissue of hyperinsulinaemic animals . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We examined the role of the mammalian target of rapamycin and ribosomal p70S6 kinase ( p70S6K ) in S 1 P induced SMC migration . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We also show that insulin stimulated the phosphorylation of 4E binding protein 1 ( 4E BP 1 ) and p70S6 kinase ( p70S6K ) in a mTOR dependent manner . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here , we report that , in primary cultures of Sertoli cells isolated from prepubertal rats , FSH enhanced p70S6K enzymatic activity , in a PKA dependent manner . p70S6K was constitutively phosphorylated on Thr 389 , in a manner sensitive to inhibitors of phosphatidyl inositide 3 kinase and mammalian target of rapamycin . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We report that late in a simian virus 40 ( SV 40 ) infection in CV 1 cells , there are significant decreases in phosphorylations of two mammalian target of rapamycin ( mTOR ) signaling effectors , the eIF4E binding protein ( 4E BP 1 ) and p 70 S6 kinase ( p70S6K ) . ^^^ Serum starved primary African green monkey kidney ( AGMK ) cells also showed decreased phosphorylations of mTOR , 4E BP 1 , and p70S6K at late times in infection ( 48 h postinfection [ hpi ] ) . ^^^ The data suggest that during SV 40 lytic infection in monkey cells , the phosphorylations of p70S6K , S 6 , and eIF4G are increased early in the infection ( 12 and 24 hpi ) , but late in the infection ( 48 hpi ) , the phosphorylations of mTOR , p70S6K , and 4E BP 1 are dramatically decreased by a mechanism mediated , at least in part , by small t antigen . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
RESULTS : In the hypertrophic muscle of MLC / mlgf 1 mice , we observed increased phosphorylation of phosphoinositide dependent protein kinase 1 ( PDK 1 ; 53 % increase ) , the mammalian target of rapamycin ( mTOR ; 112 % increase ) , and p 70 S6 kinase ( p70S6K ) ( 254 % increase ) but no significant change in Akt phosphorylation ( 4 % decrease ) . ^^^ Insulin like growth factor 1 mediated skeletal muscle hypertrophy is characterized by increased mTOR p70S6K signaling without increased Akt phosphorylation . ^^^ CONCLUSION : Persistent overexpression of IGF 1 in mice skeletal muscle results in hypertrophy , which is likely mediated via the mTOR / p70S6K pathway , potentially via an Akt independent signaling pathway . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Translational control includes phosphorylation of the kinases mammalian target of rapamycin ( mTOR ) and p70S6k which modulate cell growth , proliferation and autophagy . ^^^ In this study , we analysed modifications of mTOR / p70S6k signalling in cellular and transgenic models of Alzheimer ' s disease , as well as in lymphocytes of patients and control individuals . ^^^ Abeta 1 42 produced a rapid and persistent down regulation of mTOR / p70S6k phosphorylation in murine neuroblastoma cells associated with caspase 3 activation . ^^^ Using western blottings , we found that phosphorylated forms of mTOR and p70S6k are decreased in the cortex but not in the cerebellum ( devoid of plaques ) of double APP / PS1 transgenic mice compared with control mice . ^^^ Taken together , these findings demonstrate that the mainly anti apoptotic mTOR / p70S6k signalling is altered in cellular and transgenic models of Alzheimer ' s disease and in peripheral cells of patients , and could contribute to the pathogenesis of the disease . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Hepatectomy induced immediate but transient phosphorylation of Akt , p70S6K , mTOR and GSK 3beta in LS 3 KO mice much more than in control mice . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
However , the HG induced alterations in phosphorylation of Akt , mTOR , p70s6k and GSK 3beta were significantly reversed by IGF 1 . ^^^ Protein expression of Akt , mTOR , p70s6k , GSK 3beta , SERCA2a and phospholamban was unaffected by HG , IGF 1 or rapamycin . ^^^ Collectively , our data suggest that IGF 1 may provide cardiac protection against glucose in part through a PI 3 kinase / Akt / mTOR / p70s6k dependent and calcineurin independent pathway . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Cells lacking PDK 1 show decreased activity of these protein kinases , including protein kinase B ( PKB ) and p70S6K , whereas mTOR activity remains largely unaffected . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Mechanistic studies showed that inhibition of the mTOR pathway by rapamycin alone sufficiently suppressed the phosphorylation of the downstream molecules p70S6K and 4E BP 1 , but only caused a moderate cytostatic effect . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
As expected , rapamycin inhibited the phosphorylation of mTOR substrates , p70S6K and 4EBP1 , and BAY 43 9006 inhibited phosphorylation of ERK , which is dependent on B Raf activity . ^^^ We also observed unexpected rapamycin inhibition of the phosphorylation of ERK , as well as BAY 43 9006 inhibition of the phosphorylation of mTOR substrates , p70S6K and 4EBP1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Activation of mTOR leads to increased protein synthesis through phosphorylation of p70S6K and 4E BP 1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The phosphorylation of FAK , mTOR , p70S6K , and PDK 1 were elevated in both breast cancer cell lines , whereas the phosphorylation of AKT , EGFR , ErbB2 / Her2 , PDGFR , Shc , and Stat 3 were elevated in only one breast cancer line compared to normal primary mammary epithelial cells and telomerase immortalised breast epithelial cells . ^^^ Elevated phosphorylation of PDK 1 , AKT , mTOR , p70S6K , S 6 , EGFR , and Stat 3 were highly associated with invasive breast tumours ( P < 0 . 05 ) . ^^^ This is the first report demonstrating phosphorylation of PDK 1 is frequently elevated in breast cancer with concomitantly increased phosphorylation of downstream kinases , including AKT , mTOR , p70S6K , S 6 , and Stat 3 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Treatment of cells with the phosphatidylinositol 3 kinase ( PI3K ) inhibitors wortmannin and LY 294002 [ 2 ( 4 morpholinyl ) 8 phenyl 4H 1 benzopyran 4 one ] or rapamycin , an inhibitor of mammalian target of rapamycin and ribosomal p 70 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 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Reflecting its critical role in integrating cell growth and division with the cellular nutritional environment , the mammalian target of rapamycin * ( mTOR ) is a highly conserved downstream effector of the phosphatidylinositol 3 kinase ( PI3K ) / Akt ( protein kinase B ) signaling pathway . mTOR activates both the 40S ribosomal protein S 6 kinase ( p70s6k ) and the eukaryotic initiation factor 4E binding protein 1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
To investigate this hypothesis , skeletal muscles ( ex vivo ) were stimulated with nutrients or intermittent mechanical stretch and the phosphorylation of p70S6k [ P p 70 ( 389 ) ] , PKB [ P PKB ] , mTOR [ P mTOR ( 2481 ) ] , and p 38 [ P p 38 ] was assessed . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Dendritic complexity was reduced by inhibition of PI3K and by RNAi knockdown of mTOR or p 70 ribosomal S 6 kinase ( p70S6K , an effector of mTOR ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The Akt / mammalian target of rapamycin ( mTOR ) / ribosomal protein S 6 kinase ( p70S6K ) pathway is considered a central regulator of protein synthesis and of cell proliferation , differentiation , and survival . ^^^ However , the role of the Akt / mTOR / p70S6K pathway in lung carcinoma remains unknown . ^^^ Herein , we explore the role of the Akt / mTOR / p70S6K pathway in fibronectin induced NSCLC cell growth . ^^^ Rapamycin , an inhibitor of mTOR , blocked the fibronectin induced phosphorylation of p70S6K and 4E BP 1 . ^^^ Taken together , these observations suggest that fibronectin induced stimulation of NSCLC cell proliferation requires activation of the Akt / mTOR / p70S6K pathway and is associated with inhibition of LKB1 / AMPK signaling . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Altogether , our results are in line with a model in which binding of TPO to the TPO receptor ( mpl ) could activate the rapamycin sensitive PI3K AKT mTOR p70S6K pathway and its downstream targets in promoting megakaryocytic cell polyploidization . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The anti IGF 1 effect of troglitazone in mouse skin keratinocytes was due to , at least partially , inhibition of IGF 1 induced phosphorylation of p70S6 kinase ( p70S6K ) at Thr ( 389 ) , a site specifically phosphorylated by mammalian target of rapamycin ( mTOR ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We report here that hypoxia inhibits mRNA translation by suppressing multiple key regulators , including eIF2alpha , eEF 2 , and the mammalian target of rapamycin ( mTOR ) effectors 4EBP1 , p70S6K , and rpS 6 , independent of HIF . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
ErbB 2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin / p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells . ^^^ This was mediated through signaling events involving extracellular signal regulated kinase , phosphatidylinositol 3 kinase / Akt , mammalian target of rapamycin ( mTOR ) , and p70S6K . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In addition , rosiglitazone increased the phosphorylation of AMP activated protein kinase alpha ( AMPKalpha ) , a downstream kinase target for LKB 1 , whereas it decreased phosphorylation of p 70 ribosomal protein S 6 kinase ( p70S6K ) , a downstream target of mammalian target of rapamycin ( mTOR ) . ^^^ Taken together , these findings show that rosiglitazone , via up regulation of the PTEN / AMPK and down regulation of the Akt / mTOR / p70S6K signal cascades , inhibits NSCLC cell proliferation through PPARgamma dependent and PPARgamma independent signals . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
However , the mTOR / p70s6K pathway inhibitor rapamycin did not alter bradykinin induced GSK 3beta phosphorylation and bradykinin failed to alter phosphorylation of either mTOR or p70s6K at reperfusion . ^^^ The PI 3 kinase / Akt pathway and ERK , but not the mTOR / p70s6K pathway account for the suppression of GSK 3beta by bradykinin . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here , we investigated the role of the mTOR p70S6K and the ERK1 / 2 p70S6K pathways in rat striatal and hippocampal synaptoneurosomes after group 1 mGluR stimulation . ^^^ Our findings show that ( S ) 3 , 5 dihydroxyphenylglycine ( DHPG ) increases significantly the activation of mTOR and p70S6K ( Thr 389 , controlled by mTOR ) in both brain areas . ^^^ The mTOR activation is dose dependent and requires the stimulation of mGluR 1 subtype receptors as for the p70S6K activation observed in striatum and hippocampus . ^^^ These results demonstrate that group 1 mGluRs are coupled to mTOR p70S6K and ERK1 / 2 p70S6K pathways in striatal and hippocampal synaptoneurosomes . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Pretreatment of NHEK with PFE ( 60 100 microg / mL ) for 24 h before exposure to UVA resulted in a dose dependent inhibition of UVA mediated phosphorylation of STAT 3 at Tyr 705 , AKT at Ser 473 and ERK1 / 2 . mTOR , structurally related to PI3K , is involved in the regulation of p70S6K , which in turn phosphorylates the S 6 protein of the 40S ribosomal subunit . ^^^ We found that UVA radiation of NHEK resulted in the phosphorylation of mTOR at Thr 2448 and p70S6K at Thr421 / Ser424 . ^^^ PFE pretreatment resulted in a dose dependent inhibition in the phosphorylation of mTOR at Thr 2448 and p70S6K at Thr421 / Ser424 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Consistent with the notion that the endomembrane may serve as a platform for the assembly of a functional Rheb / mTOR complex , treatment of cells with brefeldin A interferes with transmission of Rheb signals to p70S6K . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The presence of p Akt was accompanied by the phosphorylation of p 27 ( kip 1 ) , FRKHL 1 , MDM 2 , Bad , mTOR , and p70S6K . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mTOR signaling pathway was suppressed in tumor cells and in subcutaneous gliomas treated with hTERT Ad compared with GFP Ad or no treatment as shown by reduced phosphorylation of mTOR ' s downstream target p70S6 kinase ( p70S6K ) . hTERT Ad treatment of mice ( n = 7 ) slowed growth of subcutaneous gliomas ( mean tumor volume = 39 mm 3 , 95 % confidence interval [ CI ] = 23 to 54 mm 3 ) compared with GFP Ad treatment ( n = 7 ) ( mean tumor volume = 200 mm 3 , 95 % CI = 149 to 251 mm 3 ) at day 7 ( volume difference = 161 mm 3 , 95 % CI = 126 to 197 mm 3 ; P < . 001 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here , we show that modulation of mTOR activity affects caveolin 1 localization and that this effect is independent of p70S6K . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Thyroid hormone stimulates protein synthesis in the cardiomyocyte by activating the Akt mTOR and p70S6K pathways . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here , we provide evidence that mTOR signaling phosphoproteins , including mTOR , eukaryotic initiation factor 4E binding protein 1 , p70S6K , and ribosomal protein S 6 , are highly phosphorylated in ALK+ ALCL cell lines and tumors . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Furthermore , cotreatment with rapamycin , a specific mTOR inhibitor , and troglitazone additively inhibited both p70S6K activity and protein synthesis , suggesting that the inhibitory effects of troglitazone are not mediated by mTOR . ^^^ In conclusion , our data demonstrate for the first time that troglitazone ( and perhaps other TZDs ) acutely decreases p70S6K activity through a PP2A dependent mechanism that is independent of mTOR and PPARgamma , leading to the inhibition of protein synthesis in endothelial cells . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Prolactin activates mammalian target of rapamycin through phosphatidylinositol 3 kinase and stimulates phosphorylation of p70S6K and 4E binding protein 1 in lymphoma cells . ^^^ The activated mTOR kinase phosphorylates / activates ribosomal protein S 6 kinase ( p70S6K ) and phosphorylates / inactivates eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) , resulting in the initiation of translation and cell cycle progression . ^^^ This study showed that PRL stimulated the phosphorylation of mTOR , p70S6K , Akt , and Jak 2 kinases in a dose and time dependent manner in PRL dependent rat Nb 2 lymphoma cells . ^^^ PRL stimulated phosphorylation of mTOR was detected as early as 10 min , closely following the phosphorylation of Akt ( upstream of mTOR ) , but preceding that of the downstream p70S6K . ^^^ These results suggested that p70S6K and 4E BP 1 were substrates of PP2A and the inhibition of mTOR promoted their dephosphorylation by PP2A . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
While expression of CA Akt caused a constitutive activation of p70S6 kinase ( p70S6K ) in HC 11 cells , the inhibition of either PI 3 kinase or mTOR abolished the activation of p70S6K by EGF . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Immunopurified mammalian target of rapamycin phosphorylates and activates p 70 S6 kinase alpha in vitro . p 70 S6 kinase alpha ( p70alpha ) is activated in vivo through a multisite phosphorylation in response to mitogens if a sufficient supply of amino acids is available or to high concentrations of amino acids per se . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Raptor , a binding partner of target of rapamycin ( TOR ) , mediates TOR action . mTOR controls cell growth , in part by regulating p 70 S6 kinase alpha ( p70alpha ) and eukaryotic initiation factor 4E binding protein 1 ( 4EBP1 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Recent reports including our study have demonstrated the possible interplay between mTOR and AMPK signaling pathways , supporting a model in which mitochondrial dysfunction caused by the mitochondrial inhibitors or ATP depletion inhibits activation of p 70 S6 kinase alpha ( p70alpha ) , a downstream effector of mTOR , by activating AMPK . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here , we show that hamartin and tuberin function together to inhibit mammalian target of rapamycin ( mTOR ) mediated signaling to eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) and ribosomal protein S 6 kinase 1 ( S6K1 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
BACKGROUND : The mammalian target of rapamycin , mTOR , is a serine / threonine kinase that controls cell growth and proliferation via the translation regulators eukaryotic initiation factor 4E ( eIF4E ) binding protein 1 ( 4E BP 1 ) and ribosomal protein S 6 kinase 1 ( S6K1 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Interaction of hamartin with tuberin forms a heterodimer that inhibits signaling by the mammalian target of rapamycin to its downstream targets : eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) and ribosomal protein S 6 kinase 1 ( S6K1 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Mammalian target of rapamycin ( mTOR ) is a key regulator of cell growth acting via two independent targets , ribosomal protein S 6 kinase 1 ( S6K1 ) and 4EBP1 . ^^^ Mammalian target of rapamycin ( mTOR ) is a key regulator of cell growth acting via two independent targets , ribosomal protein S 6 kinase 1 ( S6K1 ) and 4EBP1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
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 RAD 001 , indicated that RAD 001 treatment blocked phosphorylation of the translational repressor eukaryotic initiation factor 4E binding protein 1 and inactivated the translational activator ribosomal protein S 6 kinase 1 ( S6K1 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Phosphorylation of AMPK either in vivo or in situ was associated with a repression of protein synthesis as well as decreased phosphorylation of a number of targets of mTOR signaling including ribosomal protein S 6 kinase 1 , eukaryotic initiation factor ( eIF ) 4G , and eIF4E binding protein ( 4E BP ) 1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Characterization of a conserved C terminal motif ( RSPRR ) in ribosomal protein S 6 kinase 1 required for its mammalian target of rapamycin dependent regulation . ^^^ The mammalian target of rapamycin , mTOR , is a Ser / Thr kinase that promotes cell growth and proliferation by activating ribosomal protein S 6 kinase 1 ( S6K1 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Activation and phosphorylation of S6K1 ( ribosomal protein S 6 kinase 1 ) and phosphorylation of eIF4E ( eukaryotic initiation factor 4E ) binding protein ( both are mTOR targets ) were also inhibited by MKP 3 , suggesting that ERK is also required for the activation of mTOR signalling . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Intriguingly , the homozygous deletion of ribosomal protein S 6 kinase 1 ( S6K1 ) , an mTOR target , in mice results in hypoinsulinemia and glucose intolerance . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In the present study , we examined the phosphorylation state of mTOR , eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) , and ribosomal protein S 6 kinase 1 ( S6K1 ) in liver of rats with or without activation of the BCKDC by clofibrate treatment . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Recent studies have revealed that ribosomal protein S 6 kinase 1 , S6K1 , an effector of mTOR , is sensitive to both insulin and nutrients , including amino acids . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Activation of positive regulators of protein synthesis , mammalian target of rapamycin ( mTOR ) , ribosomal protein S 6 kinase 1 ( S6K1 ) , and eIF4E binding protein 1 ( 4E BP 1 ) decreased with age in muscle but not liver . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The decline in protein synthesis and changes in mRNA translation were associated with a repression of the mammalian target of rapamycin ( mTOR ) signaling pathway , as indicated by increased association of Hamartin with Tuberin , increased association of regulatory associated protein of mTOR with mTOR , and dephosphorylation of the downstream targets ribosomal protein S 6 kinase 1 and eukaryotic initiation factor 4E binding protein 1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The present experiments were performed to determine whether PGF2alpha stimulates the mammalian target of rapamycin ( mTOR ) / ribosomal protein S 6 kinase 1 ( S6K1 ) signaling pathway in steroidogenic luteal cells . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Treatment of cells with inhibitors of phosphatidylinositol 3 kinase , or FRAP ( FKBP 12 / rapamycin associated protein ) blocks integrin mediated activation of S6K . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In summary , our results indicate that PHAS 1 and 2 are controlled by the mammalian target of rapamycin and p 70 ( S6K ) signaling pathway and that in 3T3 L 1 adipocytes this pathway is inhibited by increased cAMP . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here , we show that RAFT 1 directly phosphorylates p 70 ( S6k ) , 4E BP 1 , and 4E BP 2 and that serum stimulates RAFT 1 kinase activity with kinetics similar to those of p 70 ( S6k ) and 4E BP 1 phosphorylation . ^^^ RAFT 1 phosphorylates p 70 ( S6k ) on Thr 389 , a residue whose phosphorylation is rapamycin sensitive in vivo and necessary for S 6 kinase activity . ^^^ RAFT 1 phosphorylates p 70 ( S6k ) much more effectively than 4E BP 1 , and the phosphorylation sites on the two proteins show little homology . ^^^ This raises the possibility that , in vivo , an unidentified kinase analogous to p 70 ( S6k ) is activated by RAFT 1 phosphorylation and acts at the rapamycin sensitive phosphorylation sites of 4E BP1 . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We propose that amino acids , in particular branched chain amino acids , may promote beta cell proliferation either by stimulating phosphorylation of PHAS 1 and p 70 ( s6k ) via the mammalian target of rapamycin pathway and / or by facilitating the proliferative effect mediated by growth factors such as insulin and IGF I . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The relationships between cellular sensitivity to rapamycin , drug accumulation , expression of mammalian target of rapamycin ( mTOR ) , and inhibition of growth factor activation of ribosomal p70S6 kinase ( p 70 ( S6k ) ) and dephosphorylation of pH acid stable protein 1 ( eukaryotic initiation factor 4E binding protein ) were examined . ^^^ The activity of p 70 ( S6k ) , activated downstream of mTOR , was similar in four cell lines ( range , 11 . 75 41 . 8 pmol / 2 10 10 ( 6 ) cells / 30 min ) , but activity was equally inhibited in cells that were highly resistant to rapamycin induced growth arrest . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
These findings support the interpretation that increasing cAMP attenuates the effects of insulin on PHAS 1 , p 70 ( S6K ) , and other downstream targets of the mTOR signaling pathway by inhibiting the phosphorylation and activation of mTOR . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Neither basal nor insulin stimulated p 70 ( S6K ) activity , a signalling element lying downstream of mTOR , were modified by STZ diabetes . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In human T lymphoblastoid cells , downstream signaling events of mammalian target of rapamycin ( mTOR ) , including the activity of p 70 ( s6k ) and phosphorylation of eukaryotic initiation factor 4E binding protein 1 , were dependent on amino acid concentration in the culture media , whereas other growth related protein kinases were not . ^^^ Moreover , amino acid concentration similarly affected the p 70 ( s6k ) activity , which was dependent on a rapamycin resistant mutant ( S2035I ) of mTOR . ^^^ These data indicate that mTOR is required for amino acid dependent activation of p 70 ( s6k ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Cyclin D 1 expression mediated by phosphatidylinositol 3 kinase through mTOR p 70 ( S6K ) independent signaling in growth factor stimulated NIH 3T3 fibroblasts . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Depriving cells of amino acids or treating them with the small molecule rapamycin inhibits FRAP and results in rapid dephosphorylation and inactivation of the translational regulators 4E BP 1 ( eukaryotic initiation factor 4E binding protein 1 ) and p 70 ( s6k ) ( the 70 kDa S 6 kinase ) . ^^^ Data published recently have led to the view that FRAP acts as a traditional mitogen activated kinase , directly phosphorylating 4E BP 1 and p 70 ( s6k ) in response to mitogenic stimuli . ^^^ We present evidence that FRAP controls 4E BP 1 and p 70 ( s6k ) phosphorylation indirectly by restraining a phosphatase . ^^^ FRAP also is shown to phosphorylate PP2A in vitro , consistent with a model in which phosphorylation of PP2A by FRAP prevents the dephosphorylation of 4E BP 1 and p 70 ( s6k ) , whereas amino acid deprivation or rapamycin treatment inhibits FRAP ' s ability to restrain the phosphatase . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We demonstrate that the COOH terminal tail is required for FRAP kinase activity and for signaling to the translational regulator p 70 ( s6k ) ( ribosomal subunit S 6 kinase ) . ^^^ FRAP autophosphorylation is blocked completely by wortmannin treatment but not by rapamycin treatment , amino acid deprivation , or serum withdrawal , treatments that lead to acute dephosphorylation of eIF4E binding protein ( 4E BP 1 ) and p 70 ( s6k ) . ^^^ These results suggest that FRAP responsive dephosphorylation of 4E BP 1 and p 70 ( s6k ) occurs through a mechanism other than inhibition of intrinsic FRAP kinase activity . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The rapamycin and FKBP target 1 ( RAFT 1 ) , also known as FKBP 12 rapamycin associated protein ( FRAP , mTOR ) , regulates the p70S6 kinase ( p 70 ( S6k ) ) and the eukaryotic initiation factor 4E ( eIF4E ) binding protein 1 ( 4E BP 1 ) . ^^^ The present results demonstrate that c Abl binds directly to RAFT 1 and phosphorylates RAFT 1 in vitro and in vivo . c Abl inhibits autophosphorylation of RAFT 1 and RAFT 1 mediated phosphorylation p 70 ( S6k ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapamycin , an inhibitor of the mammalian target of rapamycin ( mTOR ) , and wortmannin , a phosphatidylinositol 3 kinase inhibitor , blocked flow induced pp 70 ( S6k ) activation ; FK 506 , a rapamycin analog with minimal mTOR inhibitory activity , and PD 98059 , an inhibitor of the flow sensitive mitogen activated protein kinase pathway , had no effect . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Hyperphosphorylation of p 70 ( s6k ) and 4E BP 1 in response to insulin or amino acids is mediated through the mammalian target of rapamycin ( mTOR ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
FKBP 12 rapamycin associated protein ( FRAP ; also named mTOR or RAFT 1 ) , a member of the ataxia telangiectasia mutated ( ATM ) related kinase family , governs a rapamycin sensitive membrane to cytoplasm signaling cascade that modulates translation initiation via p 70 S6 kinase ( p 70 ( s6k ) ) and eIF 4E binding protein 1 ( 4E BP 1 ) . ^^^ Inhibition of FRAP nuclear export by LMB coincides with diminished p 70 ( s6k ) activation and 4E BP 1 phosphorylation . ^^^ Further investigation by altering FRAP ' s nuclear shuttling activity with exogenous nuclear import and export signals has yielded results that are consistent with a direct link between nuclear shuttling of FRAP and mitogenic stimulation of p 70 ( s6k ) activation and 4E BP 1 phosphorylation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We found that both FRAP and insulin activated p 70 S6 kinase ( p 70 ( s6k ) ) serine phosphorylated IRS 1 between residues 511 and 772 ( IRS 1 ( 511 772 ) ) . ^^^ Taken together , these data indicate that FRAP , but not p 70 ( s6k ) , is a likely physiologic IRS 1 serine kinase that negatively regulates JAK 1 dependent IRS 1 tyrosine phosphorylation and suggests that FRAP may modulate IRS dependent cytokine signaling . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
BACKGROUND : The mTOR translational control pathway that signals to the P70 / P85 S 6 kinase ( pp 70 ( S6k ) ) is essential for mitogenesis . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Both amino acid and insulin activations of p 70 ( S6k ) involve a rapamycin sensitive step that involves the mammalian target of rapamycin ( mTOR , also known as FRAP and RAFT ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The decreases in the phosphorylation of 4E BP 1 and p 70 ( S6K ) did not result from a reduced abundance of mammalian target of rapamycin ( mTOR ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
FRAP has serine / threonine kinase activity and mediates the cellular response to mitogens through signaling to p70s6 kinase ( p 70 ( s6k ) ) and 4E BP 1 , resulting in an increase in translation of subsets of cellular mRNAs . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Structure / function analysis using mutant forms of S6K indicates that Ro 31 6045 inhibition is independent of the upstream activator mTOR . ^^^ Ro 31 6045 will prove useful in elucidating the complex activation mechanism of S6K and its independence from mTOR will allow confirmation of functional data obtained using the mTOR inhibitor rapamycin . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In human growth factor independent MM cell lines OPM 2 and RPMI 8226 , we show that the PI 3 K inhibitors LY 294002 and Wortmannin strongly inhibited cell proliferation , whereas inhibition of the mammalian Target Of Rapamycin ( mTOR ) / P70 S 6 kinase ( P 70 ( S6K ) ) pathway with rapamycin or of the Mitogen Activated Protein Kinase ( MAPK ) pathway with PD 98059 had minimal effect on proliferation . ^^^ In both cell lines , constitutive activation of the PI 3 K / Akt / FKHRL 1 , mTOR / P70 ( S6K ) and MAPK pathways was detected . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mammalian target of rapamycin ( mTOR ) is a Ser / Thr ( S / T ) protein kinase , which controls mRNA translation initiation by modulating phosphorylation of the translational regulators PHAS 1 and p 70 ( S6K ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Ultraviolet induced phosphorylation of p 70 ( S6K ) at Thr ( 389 ) and Thr ( 421 ) / Ser ( 424 ) involves hydrogen peroxide and mammalian target of rapamycin but not Akt and atypical protein kinase C . ^^^ These results demonstrated that H ( 2 ) O ( 2 ) , phosphatidylinositol 3 kinase , and mammalian target of rapamycin were important players for UV induced p 70 ( S6k ) phosphorylation at Thr ( 389 ) and Thr ( 421 ) / Ser ( 424 ) , whereas Akt and atypical protein kinase C were not involved in this activation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Transfection of PTEN into the PC 3 cells decreased the activation of Akt and the downstream mTOR regulated 70 kDa S 6 ( p 70 ( s6k ) ) kinase and reversed the resistance to doxorubicin in these cells , indicating that changes in PTEN status / Akt activation modulate the cellular response to doxorubicin . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Similarly , complete inhibition of mammalian target of rapamycin ( mTOR ) and its effector S6K by rapamycin in various cell lines has only a mild repressive effect on the translation of TOP mRNAs . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We reported that the mitogen activated protein / extracellular signal regulated kinase kinase ( MEK ) inhibitor U 0126 inhibited anchorage independent growth of Ki ras transformed rat fibroblasts by simultaneously blocking both extracellular signal regulated kinase ( ERK ) and mammalian target of rapamycin ( mTOR ) p 70 ( S6K ) pathways . ^^^ The results indicate that concurrent inhibition of MEK ERK and mTOR p 70 ( S6K ) pathways induces apoptosis in MDA MB 231 and HBC 4 cells when cells are deprived of anchorage but not when anchored . ^^^ Inhibitors of MEK ERK and mTOR p 70 ( S6K ) pathways may provide a therapeutic strategy to selectively target neoplasms proliferating at ectopic locations , with acceptable effects on normal cells in their proper tissue context . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rheb stimulates the phosphorylation of mTOR and plays an essential role in regulation of S6K and 4EBP1 in response to nutrients and cellular energy status . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We demonstrate that rapamycin inhibits phosphorylation of downstream targets of mTOR such as p 70 ( S6K ) kinase and 4E BP 1 translation repressor . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The cytokine signaling intermediates for mTOR / ribosomal protein S 6 kinase ( S6K ) activation include phosphatidylinositol 3 kinase , Akt , Erks and geranylgeranylated proteins . ^^^ Inhibitors of these intermediates suppress cytokine activation of S6K and induce Ocl apoptosis . mTOR regulates protein translation acting via S6K , 4E BP 1 and S 6 . ^^^ This study thus identifies mTOR / S6K as an essential signaling pathway engaged in the stimulation of cell survival in osteoclasts . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Since mTOR activates both the 40S ribosomal protein S 6 kinase ( ( p ) 70 ( s6k ) ) and the eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) , RAP blocks activation of these downstream signaling elements , which results in cell cycle arrest in the G 1 arrest . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
PI3K regulates cell cycle through AKT , mTOR to p 70 ( S6K ) . ^^^ These results suggest that PI3K mediates G ( 1 ) cell cycle progression and cyclin expression through the activation of AKT / mTOR / p70 ( S6K ) signaling pathway in the prostate cancer cells . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Tsc 2 ( / ) TP 53 ( / ) cells , as well as tumors from Tsc 2 ( + / ) mice , display an mTOR activation signature with constitutive activation of S6K , which is reverted by treatment with rapamycin . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Recent studies established that amino acids and insulin induce p 70 S6 kinase ( p 70 ( S6k ) ) phosphorylation by mTOR , involved in translational control of protein synthesis . ^^^ In isolated rat hepatocytes , both regulatory amino acids ( RegAA ) and insulin coordinately activated p 70 ( S6k ) phosphorylation , which was completely blocked by rapamycin , an mTOR inhibitor . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Mitogens activate protein translation through phosphorylation of p7S6 kinase ( p 70 ( S6K ) ) and eIF4E binding protein 1 ( 4E BP 1 ) mediated by the mammalian target of rapamycin ( mTOR ) or phosphoinositide 3 kinase ( PI3K ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Stimulation by any of these agents is inhibited by the bacterial macrolide rapamycin , which binds to and inactivates the mammalian target of rapamycin , an S6K kinase . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
By contrast , the major translational control pathway involving Akt , mTOR , and S6K was strongly regulated by fasting and refeeding . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Using a phospho specific antibody to mammalian target of rapamycin ( mTOR ) , we find that activated mTOR is enriched at the actin arc , suggesting that activation of the p 70 ( S6K ) signaling pathway is important to cell migration . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In addition , we examined whether mammalian target of rapamycin signaling controls S6K activation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The stimulation of protein synthesis by ANG 2 in cSMCs was blocked by the immunosuppressant rapamycin , which is an inhibitor of the mammalian target of rapamycin ( mTOR ) signaling pathway that includes the 70 kDa S 6 kinase ( p 70 ( S6k ) ) and plays a key role in cell growth . ^^^ In conclusion , we have shown that ANG 2 activates components of the rapamycin sensitive mTOR signaling pathway in human cSMCs and involves activation of phosphatidylinositol 3 kinase , p 70 ( S6k ) , and eukaryotic initiation factor 4E , which leads to activation of protein synthesis . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The effects of AICAR and the toxins were rapamycin resistant ; in contrast , amino acids induced an S6K tail phosphorylation that was rapamycin sensitive , suggesting mediation by the protein kinase mammalian target of rapamycin ( mTOR ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Inappropriate activation of the TSC / Rheb / mTOR / S6K cassette induces IRS1 / 2 depletion , insulin resistance , and cell survival deficiencies . ^^^ Loss of function of the TSC 1 TSC2 complex , which acts as a Rheb GAP , yields constitutive , unrestrained signaling from the cell growth machinery comprised of Rheb , mTOR , and S6K . ^^^ We demonstrate herein that constitutive activation of the Rheb / mTOR / S6K cassette , whether by genetic deletion of TSC 1 or TSC 2 or by ectopic expression of Rheb , is sufficient to induce insulin resistance . ^^^ Our results suggest that inappropriate activation of the Rheb / mTOR / S6K pathway imposes a negative feedback program to attenuate IRS dependent processes such as cell survival . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Combined treatment also resulted in pronounced reductions in levels of phospho Akt , glycogen synthase kinase 3 ( GSK 3 ) , p 70 ( S6K ) , mammalian target of rapamycin ( mTOR ) , forkhead transcription factor ( FKHR ) , caspase 9 , and Bad . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Disruption of the TSC1 / TSC2 complex through loss of TSC 1 or TSC 2 blocks the effects of hypoxia on mTOR , as measured by changes in the mTOR targets S6K and 4E BP 1 , and results in abnormal accumulation of Hypoxia inducible factor ( HIF ) . ^^^ Disruption of REDD 1 abrogates the hypoxia induced inhibition of mTOR , and REDD 1 overexpression is sufficient to down regulate S6K phosphorylation in a TSC1 / TSC2 dependent manner . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Specific interaction between S6K1 and CoA synthase : a potential link between the mTOR / S6K pathway , CoA biosynthesis and energy metabolism . ^^^ This study uncovers a potential link between mTor / S6K signaling pathway and energy metabolism through CoA and its thioester derivatives , but its physiological relevance should be further elucidated . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The aim of this study was to determine whether the phosphatidylinositol 3 kinase ( PI3K ) dependent mammalian target of rapamycin ( mTOR ) eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) signal pathway and S 6 kinase ( S6K ) , the major element of the mTOR pathway , play a role in the enhanced vascular endothelial cell ( EC ) proliferation induced by cyclic strain . ^^^ These data suggest that the PI3K dependent S6K mTOR 4E BP 1 signal pathway may be critically involved in strain induced bovine aortic EC proliferation . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Basal rates of MPS were indistinguishable , but the elderly showed less anabolic sensitivity and responsiveness of MPS to EAA , possibly due to decreased intramuscular expression , and activation ( phosphorylation ) after EAA , of amino acid sensing / signaling proteins ( mammalian target of rapamycin , mTOR ; p 70 S6 kinase , or p 70 ( S6k ) ; eukaryotic initiation factor [ eIF ] 4BP 1 ; and eIF2B ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Mammalian target of rapamycin ( mTOR ) mediates a signaling pathway that couples amino acid availability to S 6 kinase ( S6K ) activation , translational initiation and cell growth rate , participating to a versatile checkpoint that inspects the energy status of the cell . ^^^ Mammalian target of rapamycin ( mTOR ) mediates a signaling pathway that couples amino acid availability to S 6 kinase ( S6K ) activation , translational initiation and cell growth rate , participating to a versatile checkpoint that inspects the energy status of the cell . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
PURPOSE : mTOR and P 70 S6 kinase ( S6K ) play a key role in regulating protein translation . ^^^ The role of mTOR and S6K in hepatocellular carcinoma has not been investigated , but this pathway is of particular interest because an effective inhibitor , rapamycin , is available . ^^^ EXPERIMENTAL DESIGN : Total and phosphorylated mTOR and S6K protein expression were studied by immunohistochemistry in hepatocellular carcinomas ( n = 73 ) , fibrolamellar carcinomas ( n = 13 ) , and hepatic adenomas ( n = 15 ) . ^^^ Phospho mTOR positivity correlated with increased expression of total S6K , which was found in 45 % of cases . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mammalian target of rapamycin ( mTOR ) is a serine / threonine kinase that plays an essential role in cell growth control . mTOR stimulates cell growth by phosphorylating p 70 ribosomal S 6 kinase ( S6K ) and eukaryote initiation factor 4E binding protein 1 ( 4EBP1 ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
This finding , together with earlier work , strongly suggests that a major form of negative feedback inhibition of PI3K results from activated growth signalling via mammalian target of rapamycin ( mTOR ) and the p 70 S6 kinase ( S6K ) a pathway that could have consequences for the development of type 2 diabetes and tuberous sclerosis complex . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Subsequently , we showed that treatment with FN induced a rapid activation of mTOR as well as its downstream effector , S 6 kinase ( S6K ) . ^^^ A blocking antibody to alpha ( 5 ) beta ( 3 ) inhibited FN induced mTOR / S6K activation as well as E 47 cell chemotaxis , implicating alpha ( 5 ) beta ( 3 ) as the integrin receptor responsible for initiating FN induced migration . ^^^ Moreover , preincubation of E 47 cells with wortmannin or LY 294002 blocked FN induced mTOR / S6K activation , demonstrating that phosphatidylinositol 3 kinase ( PI3K ) plays a critical role in this rapamycin sensitive signaling pathway . ^^^ Taken together , our data demonstrate that rapamycin inhibits FN induced SMC migration through a pathway that involves at least alpha ( 5 ) beta ( 3 ) integrin , PI3K , mTOR , and S6K . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In addition , radicicol , an inhibitor of heat shock protein 90 ( Hsp 90 ) , and rapamycin , an inhibitor of the mammalian target of rapamycin ( mTOR ) , blocked IL 2 induced hTERT activity and nuclear translocation of hTERT but not hTERT mRNA expression . hTERT was coimmunoprecipitated with Akt , Hsp 90 , mTOR , and p 70 S6 kinase ( S6K ) , suggesting that these molecules form a physical complex . ^^^ Immunoprecipitates of Akt , Hsp 90 , mTOR , and S6K from IL 2 stimulated NK 92 cells contained telomerase activity . ^^^ These results indicate that IL 2 stimulation induces hTERT activation and that the mechanism of IL 2 induced hTERT activation involves transcriptional or posttranslational regulation through the pathway including PI3K / Akt , Hsp 90 , mTOR , and S6K in NK cells . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Low dose IR inhibited the phosphorylation of p 70 ( S6K ) , a molecule downstream of the mammalian target of rapamycin associated with autophagy in M059J cells but not in M059K cells . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In Jurkat cells , the decreased cell growth rate associated with a long lasting deactivation of the mammalian target of rapamycin ( mTOR ) / p70 ribosomal S 6 kinase ( S6K ) signaling pathway generates a cell population of progressively reduced cellular mass and size . ^^^ Cell size reduction induced by inhibition of the mTOR / S6K signaling pathway protects Jurkat cells from apoptosis . ^^^ Protection faded when reactivation of the mTOR / S6K pathway promoted the cell recovery to normal size . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Significantly , rapamycin completely inhibited the phosphorylation of p 70 ( S6K ) , an mTOR regulated kinase implicated in the control of proliferation , but had no effect on collagen or total protein synthesis . ^^^ We show that p 70 ( S6K ) is markedly inhibited in rapamycin arrested ISR cells , suggesting that regulation of its upstream kinase , mTOR , is important for the control of proliferation in ISR cells . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Mammalian target of rapamycin ( mTOR ) , a serine / threonine kinase , regulates cell growth and proliferation in part via the activation of p 70 S6 kinase ( S6K ) . ^^^ Mammalian target of rapamycin ( mTOR ) , a serine / threonine kinase , regulates cell growth and proliferation in part via the activation of p 70 S6 kinase ( S6K ) . ^^^ In human lung epithelial adenocarcinoma ( A 549 ) cells , LY 303511 , like rapamycin , inhibited mTOR dependent phosphorylation of S6K , but not PI3K dependent phosphorylation of Akt . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
These effects of IGF 1 were associated with increased phosphorylation of Akt , GSK 3beta , and the mTOR downstream targets p 70 ( S6K ) and 4E BP 1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Endogenous REDD 1 is induced following energy stress , and REDD 1 / cells are highly defective in dephosphorylation of the key mTOR substrates S6K and 4E BP 1 following either ATP depletion or direct activation of the AMP activated protein kinase ( AMPK ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Compared with control cells , HUVEC overexpressing T cad ( T cad+ HUVEC ) had higher phosphorylation levels for phosphatidylinositol 3 kinase ( PI3K ) target Akt and mTOR target p 70 ( S6K ) ( survival pathway regulators ) , but lower levels for p38MAPK ( death pathway regulator ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The downstream effectors of mTOR , p 70 S6 kinase ( S6K ) and 4E binding protein 1 ( 4E BP 1 ) , are phosphorylated by TPO in a rapamycin and LY 294002 sensitive manner . ^^^ Part of the effect of the phosphatidyl inositol 3 kinase pathway in regulating megakaryopoiesis may be mediated by the mTOR / S6K / 4E BP 1 pathway . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The p 70 S6 ribosomal protein kinase 1 ( S6K ) is a substrate and effector of the mammalian target of rapamycin ( mTOR ) . ^^^ The mTOR / S6K pathway is implicated in cancer and metabolic disorders . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Kidneys were analysed histomorphometrically , and for the expression and phosphorylation of S6K , a well characterized target of mTOR in the regulation of cell growth . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
However , when environmental conditions change , tuberin is phosphorylated and it forms a complex with hamartin is degraded , and downstream targets of mTOR , S6K , and eEF2K , can be activated . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Likewise , activation of molecules associated with hypertrophy ( AKT , mTOR , and p 70 ( S6k ) ) was diminished in mice overexpressing integrin . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Inhibition of PI 3K with low dose LY 294002 , or MAPK with PD 98059 also suppressed the mTOR / p70 S6k pathway , and correlated with the blockage of IFN gamma induced dephosphorylation of pY STAT 3 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
To this end , we used Western blotting to examine the contents and phosphorylation states of mammalian target of rapamycin ( mTOR ) and its downstream translational signalling intermediates , 70 kDa ribosomal protein S 6 kinase ( S6k ) , ribosomal protein S 6 ( rpS 6 ) , eukaryotic elongation factor 2 ( eEF 2 ) , and eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) , in conjunction with impaired growth in 1 week overloaded fast twitch plantaris muscles ( via unilateral gastrocnemius ablation ) of old ( O ; 30 months ) versus young adult ( YA ; 8 months ) male Fischer 344 10 Brown Norway rats . ^^^ The significantly ( P < or= 0 . 05 ) diminished growth ( assessed by total muscle protein content ) in overloaded O muscles ( 5 . 6 + / 1 . 7 versus 19 . 3 + / 2 . 9 % in YA ) was accompanied by significant impairments in the phosphorylation states of mTOR ( Ser 2448 ) , S6k ( impaired at the mTOR specific Thr 389 residue but not at Thr421 / Ser424 ) , rpS 6 ( Ser235 / 236 ) and 4E BP 1 ( gel shift ) , as well as deficits in total eEF 2 accretion . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Inhibitors towards tyrosine kinases , such as genistein and PP 1 , or src specific SU 6656 , but not PI3K and mTor inhibitors , lead to a reduction in tyrosine phosphorylation of S6K . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Although many links and effectors are still unknown , central components of this network include the mammalian target of rapamycin ( mTOR ) and its downstream effectors the ribosomal protein S 6 kinase ( S6K ) and the translational repressor eukaryotic initiation factor 4E binding protein . ^^^ It therefore seems that establishing the function of the phosphorylation of other effectors of mTOR or S6K will inevitably require genetic manipulation of the respective sites within these targets . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
An early signaling event activated by amino acids and growth factors in many cell types is the phosphorylation of the mammalian target of rapamycin ( mTOR ; FRAP ) , which is functionally linked to ribosomal protein s 6 kinase ( p 70 ( s6k ) ) , a kinase that plays a critical regulatory role in the translation of mRNAs and protein synthesis . ^^^ We found that 1 ) protein synthesis is required for intestinal cell migration , 2 ) mTOR / p70 ( s6k ) pathway inhibitors ( rapamycin , wortmannin , and intracellular Ca ( 2+ ) chelation ) inhibit cell migration , 3 ) ARG activates migration and mTOR / p70 ( s6k ) ( but not ERK 2 ) in migrating enterocytes , and 4 ) immunocytochemistry reveals abundant p 70 ( s6k ) staining in cytoplasm , whereas phospho p 70 ( s6k ) is virtually all intranuclear in resting cells but redistributes to the periphery on activation by ARG . ^^^ We conclude that mTOR / p70 ( s6k ) signaling is essential to intestinal cell migration , is activated by ARG , involves both nuclear and cytoplasmic events , and may play a role in intestinal repair . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The Ras related GTPase Rheb has emerged as a key player downstream of TSC 1 2 in activating signaling to mammalian target of rapamycin ( mTOR ) effectors of cell growth such as S6K and 4E BP 1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Current models suggest that AKT acts directly , or indirectly via the TSC complex , to activate the mammalian target of rapamycin ( mTOR ) as the main downstream mediator of AKT signaling . mTOR activation results in subsequent activation of S6K and STAT 3 , as well as suppression ( i . e . , phosphorylation ) of 4E BP 1 , leading to cell cycle progression and inhibition of apoptosis . ^^^ Within individual tumors , increased expression levels of p TSC 2 , p mTOR , p 4E BP 1 , p S6K , p S 6 , and p STAT 3 were found in regions defined by elevated AKT activation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Emphasis will be put on three serine / threonine kinases , mTOR , Akt and S 6 Kinase ( S6K ) , and their role in the integration of environmental cues and the coordination of muscle growth . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
RNAi mediated knockdown of RB1CC1 reduced the activation of mTOR and S6K as well as the size of HEK 293 and C2C12 cells . ^^^ Exogenous expression of RB1CC1 maintained S6K activity and cell size , and decreased TSC1 / hamartin contents under nutritionally starved conditions , which usually inhibit the mTOR S6K pathway . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Consistent with these behavioral results , biochemical analysis revealed that glucose and AICAR had opposing influences on the activation of the TSC mTOR cascade , as indicated by the phosphorylation of ribosomal S 6 kinase ( S6K ) and 4E binding protein 1 ( 4EBP1 ) , targets of mTOR . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Signaling by the PI3K / Akt / mTOR pathway profoundly affects mRNA translation through phosphorylation of downstream targets such as 4E BP and S6K . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
One such target is p70S6k1 ( S6K1 ) , a serine / threonine kinase which is inactivated by the mTOR : FKBP 12 : rapamycin complex , and which has been linked to translational control by virtue of its ability to phosphorylate the ribosomal protein S 6 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The results reveal that treating 18 h fasted pigs with rapamycin , a specific inhibitor of mTOR , before feeding prevented the activation of S6K1 and the changes in eIF4F complex formation observed in skeletal muscle and liver after feeding . ^^^ The results suggest that feeding stimulates hepatic protein synthesis through an mTOR dependent process involving enhanced eIF4F complex formation and activation of S6K1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We have recently identified S6K2 , a homolog of S6K1 , which phosphorylates S 6 in vitro and is regulated by the phosphatidylinositide 3 kinase ( PI 3 K ) and mammalian target of rapamycin pathways in vivo . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We have recently demonstrated that S6K2 is regulated similarly to S6K1 by the mammalian target of rapamycin pathway and by multiple PI 3 K pathway effectors in vivo . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
One component involved here is p 70 S6 kinase 1 ( S6K1 ) , which lies downstream of mammalian target of rapamycin , whose regulation is thought to involve phosphatidylinositol 3 kinase and protein kinase B ( PKB ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
One such mechanism involves activation of mTOR ( Fig . 1 ) . mTOR controls a myriad of downstream effectors , including RNA polymerase 1 , S6K1 , 4E BP 1 , and eEF 2 kinase . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Inhibition of mTOR by rapamycin led to fast and complete repression of S6K1 , as judged by rpS 6 phosphorylation , but to only partial and delayed repression of translational activation of TOP mRNAs . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Inhibition of the mammalian target of rapamycin with 10 ng / ml rapamycin blocked S6K1 activation and proliferation of both lines . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapamycin inhibited the mammalian target of rapamycin ( mTOR ) and the subsequent activation of p70 / p85 S 6 protein kinase 1 ( S6K1 ) by insulin , whereas amino acid depletion prevented insulin induction of these signaling molecules . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Overall , the results suggest that the blunted protein synthetic response observed in 26 vs . 7 day old neonatal pigs is due in part to decreased content and / or activity of signaling components downstream of PI 3 kinase , e . g . , PKB , mTOR , and S6K1 . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Consistent with this observation , a dominant interfering allele of the mammalian target of rapamycin , mTOR , inhibits mitogen induced Ser ( 371 ) phosphorylation and activation of S6K1 E389D ( 3 ) E , whereas wild type mTOR stimulates both responses . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
These treatments resulted in S6K1 activation with Thr 389 phosphorylation as well as mammalian target of rapamycin ( mTOR ) and S 6 protein phosphorylation . ^^^ Dominant negative c Raf expression or a MEK1 / 2 inhibitor ( U 0126 ) treatment showed a profound blocking effect only on the TPA stimulated phosphorylation of S6K1 and mTOR . ^^^ Whereas p 38 MAPK inhibitors exhibited only partial effect , MAPK phosphatase 3 expression significantly blocked the TPA stimulated S6K1 and mTOR phosphorylation . ^^^ Inhibition of mTOR with rapamycin blocked the Thr 389 but not the Thr 421 / Ser 424 phosphorylation of S6K1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
BACKGROUND : The mammalian target of rapamycin ( mTOR ) controls the translation machinery via activation of S 6 kinases 1 and 2 ( S6K1 / 2 ) and inhibition of the eukaryotic initiation factor 4E ( eIF4E ) binding proteins 1 , 2 , and 3 ( 4E BP1 / 2 / 3 ) . ^^^ The molecular basis of mTOR regulation of S6K1 and 4E BP 1 remains controversial . ^^^ The TOS motif is essential for S6K1 activation by mTOR , as mutations in this motif mimic the effect of rapamycin on S6K1 phosphorylation , and render S6K1 insensitive to changes in amino acids . ^^^ Furthermore , only overexpression of S6K1 with an intact TOS motif prevents 4E BP 1 phosphorylation by a common mTOR regulated modulator of S6K1 and 4E BP 1 . ^^^ CONCLUSIONS : S6K1 and 4E BP 1 contain a conserved five amino acid sequence ( TOS motif ) that is crucial for their regulation by the mTOR pathway . mTOR seems to regulate S6K1 by two distinct mechanisms . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Mammalian target of rapamycin ( mTOR ) controls initiation of translation through regulation of ribosomal p70S6 kinase ( S6K1 ) and eukaryotic translation initiation factor 4E ( eIF4E ) binding protein ( 4E BP ) . mTOR is considered to be located predominantly in cytosolic or membrane fractions and may shuttle between the cytoplasm and nucleus . ^^^ Mammalian target of rapamycin ( mTOR ) controls initiation of translation through regulation of ribosomal p70S6 kinase ( S6K1 ) and eukaryotic translation initiation factor 4E ( eIF4E ) binding protein ( 4E BP ) . mTOR is considered to be located predominantly in cytosolic or membrane fractions and may shuttle between the cytoplasm and nucleus . ^^^ We next investigated the cellular distribution of mTOR substrates 4E BP , S6K1 , and eIF4E . 4E BP was exclusively detected in cytoplasmic fractions in all cell lines . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Second , mutations or defects of mTOR regulated proteins , including S6K1 , 4E BP 1 , PP2A related phosphatases , and p 27 ( Kip 1 ) also render rapamycin insensitivity . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1 / eIF4E . ^^^ These data show that mTOR signals downstream to at least two independent targets , S6K1 and 4EBP1 / eIF4E , that function in translational control to regulate mammalian cell size . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Like S6K1 , the activation of S6K2 requires signaling from both the phosphatidylinositol 3 kinase and the mammalian target of rapamycin ( mTOR ) . ^^^ We demonstrate that similar to S6K1 the serum activation of S6K2 in cells is dependent on mTOR kinase activity , amino acid sufficiency , and phosphatidic acid . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapamycin deprivation and nutrient deprivation have similar effects on the activity of S 6 kinase 1 ( S6K1 ) and 4E BP 1 , two downstream effectors of RAFT 1 , but the relationship between nutrient and rapamycin sensitive pathways is unknown . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Raptor has a positive role in nutrient stimulated signaling to the downstream effector S6K1 , maintenance of cell size , and mTOR protein expression . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Phosphorylation of this motif ( FLGFT389Y ) in p 70 S6 kinase ( S6K1 ) is both rapamycin and wortmannin sensitive , suggesting a role for both mammalian target of rapamycin and phosphatidylinositol 3 kinase dependent pathways . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Although activation of wild type S6K1 and cell proliferation in TSC 2 deficient cells is dependent on the mammalian target of rapamycin ( mTOR ) , by using an S6K1 variant ( GST DeltaC S6K1 ) , which is uncoupled from mTOR signaling , we demonstrate that TSC 1 2 does not inhibit S6K1 via mTOR . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Activity of p 70 ribosomal S 6 kinase 1 ( S6K1 ) , an effector of mTOR , was increased by 3 . 8 fold in the aortic constricted heart . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Amino acid induced S6K1 activation was inhibited by LY 294002 ( PI 3 kinase inhibitor ) and rapamycin ( inhibitor of the mammalian target of rapamycin , mTOR ) , suggesting the involvement of an avian homolog of mTOR . ^^^ In conclusion , amino acids regulate S6K1 phosphorylation and activity in QM 7 cells through the mTOR / PI3 kinase pathway in an insulin independent manner . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Increased clearance of mutant huntingtin by raised glucose ( 8 g / l ) and 2DOG correlated with increased autophagy and reduced phosphorylation of mTOR , S6K1 and Akt . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Like mTOR and raptor , GbetaL participates in nutrient and growth factor mediated signaling to S6K1 , a downstream effector of mTOR , and in the control of cell size . ^^^ The binding of GbetaL to mTOR strongly stimulates the kinase activity of mTOR toward S6K1 and 4E BP 1 , an effect reversed by the stable interaction of raptor with mTOR . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Carbachol stimulated activation and phosphorylation of S6K1 at Thr 389 were prevented by rapamycin , an inhibitor of mTOR ( mammalian target of rapamycin ) , or by wortmannin , a phosphoinositide 3 kinase ( PI3K ) inhibitor . ^^^ Carbachol also stimulated the phosphorylation of eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) , a second mTOR dependent event , with similar potency to its effect on S6K1 . ^^^ This response was blocked by rapamycin , but was not markedly affected by 100 nM wortmannin , implying separate roles for mTOR and PI3K in S6K1 activation . ^^^ These observations distinguish obligatory roles for mTOR and PI3K in regulating S6K1 , but imply that minimal PI3K activity is sufficient to permit stimulation of S6K1 by other activating factors such as increased cytosolic Ca2+ concentrations , which are essential to the muscarinic receptor mediated response . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Finally , changes in 4E BP 1 and S6K1 phosphorylation were associated with altered phosphorylation of the protein kinase mammalian target of rapamycin ( mTOR ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Hamartin and tuberin control cell growth by negatively regulating S 6 kinase 1 ( S6K1 ) and eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) , potentially through their upstream modulator mammalian target of rapamycin ( mTOR ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
To begin to test the leucine oxidation hypothesis of mTOR activation , the dose dependent effects of orally administered leucine on acute activation of S6K1 ( an mTOR substrate ) and BCKD were compared using the pS 293 antibodies . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapamycin and its derivatives , CCI 779 and RAD 001 ( designated rapamycins ) , specifically inhibit the function of mTOR , leading to inactivation of ribosomal S6K1 and inhibition of cap dependent translation initiation through the 4E BP1 / eIF4E pathway . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rheb also activates S6K1 during amino acid insufficiency via a rapamycin sensitive mechanism , suggesting that Rheb participates in nutrient signaling through mTOR . ^^^ Moreover , Rheb does not activate a S6K1 mutant that is unresponsive to mTOR mediated signals , confirming that Rheb functions upstream of mTOR . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Studies using specific inhibitors and dominant negative c Raf expression in cardiomyocytes indicate that the S6K1 activation involves mTOR , MEK / ERK , and phosphatidylinositol 3 kinase pathways and is independent of protein kinase C and c Raf . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Alcohol impairs leucine mediated phosphorylation of 4E BP 1 , S6K1 , eIF4G , and mTOR in skeletal muscle . ^^^ Finally , although EtOH increased the plasma corticosterone concentration , inhibition of glucocorticoid action by RU 486 was unable to prevent EtOH induced defects in the ability of Leu to stimulate 4E BP 1 , S6K1 , and mTOR phosphorylation . ^^^ Hence , ethanol produces a leucine resistance in skeletal muscle , as evidenced by the impaired phosphorylation of 4E BP 1 , eIF4G , S6K1 , and mTOR , that is independent of elevations in endogenous glucocorticoids . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Eukaryotic initiation factor ( eIF ) 4E binding protein 1 ( 4E BP 1 ) and S 6 kinase 1 ( S6K1 ) , both downstream effectors of mTOR , were altered during recovery as well . 4E BP 1 phosphorylation was significantly elevated at 10 min ( 292 % , P < 0 . 01 ) of recovery . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mTOR / p70 S6K1 pathway regulates vascular smooth muscle cell differentiation . ^^^ Rapamycin inhibits mTOR , a signaling protein that regulates protein synthesis effectors , including p 70 S6K1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
BACKGROUND : The mammalian target of rapamycin ( mTOR ) regulates cell growth and proliferation via the downstream targets ribosomal S 6 kinase 1 ( S6K1 ) and eukaryotic translation initiation factor 4E binding protein 1 ( 4E BP 1 ) . ^^^ PLD 1 regulates mTOR signaling and mediates Cdc 42 activation of S6K1 . ^^^ In this study , we set out to test the hypotheses that phospholipase D 1 ( PLD 1 ) is an upstream regulator of mTOR and that the previously reported S6K1 activation by Cdc 42 is mediated by PLD 1 . ^^^ Using a rapamycin resistant S6K1 mutant , Cdc 42 ' s action was demonstrated to be through the mTOR pathway . ^^^ CONCLUSIONS : Our observations reveal the involvement of PLD 1 in mTOR signaling and cell size control , and provide a molecular mechanism for Cdc 42 activation of S6K1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here we demonstrate that restoration of mTOR signaling ( by using a rapamycin resistant mutant of mTOR ) rescues rapamycin inhibited G ( 1 ) phase progression , and restoration of signaling along the mTOR dependent S6K1 or 4E BP1 / eukaryotic translation initiation factor 4E ( eIF4E ) pathways provides partial rescue . ^^^ Furthermore , interfering RNA mediated reduction of S6K1 expression or overexpression of mTOR insensitive 4E BP 1 isoforms that block eIF4E activity inhibit G ( 1 ) phase progression individually and additively . ^^^ Thus , the activities of both the S6K1 and 4E BP1 / eIF4E pathways are required for and independently mediate mTOR dependent G ( 1 ) phase progression . ^^^ These data demonstrate that , as for the regulation of cell growth and cell size , the S6K1 and 4E BP1 / eIF4E pathways each represent critical mediators of mTOR dependent cell cycle control . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Moreover , although a basal amount of plasma insulin is required for leucine to enhance signaling downstream of mTOR , the concentration observed in plasma of fasted rats is sufficient to observe maximal changes in phosphorylation of 4E BP 1 and S6K1 . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Furthermore , constitutive phosphorylation of mTOR , S6K1 , the ribosomal protein S 6 , and eIF4G were also decreased in hearts from burned rats . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
PURPOSE : Rapamycin inhibits the serine threonine kinase mammalian target of rapamycin ( mTOR ) , blocking phosphorylation of p 70 S6 kinase ( S6K1 ) and 4E binding protein 1 ( 4E BP 1 ) and inhibiting protein translation and cell cycle progression . ^^^ Rapamycin inhibited the phosphorylation of S6K1 , ribosomal S 6 protein , and 4E BP 1 in rapamycin resistant as well as sensitive cells , indicating that its ability to inhibit the mTOR pathway is not sufficient to confer sensitivity to rapamycin . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Mutations that render S6K1 mTOR ( mammalian target of rapamycin ) resistant also protect S6K1 activity and phosphorylation from down regulation by Tsc1 / 2 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mammalian target of rapamycin ( mTOR ) plays an important role in regulating protein translation through phosphorylation of p 70 S6 kinase 1 ( S6K1 ) , a protein involved in ribosome biogenesis , and 4E BP 1 ( eIF 4E binding protein ) , a translation repressor . ^^^ Since low PTEN , high p AKT and high p S6K1 expression render tumors sensitive to mTOR inhibition in vitro , these criteria were used to model tumor sensitivity . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Protein synthesis in wild type livers was decreased concomitant with increased phosphorylation of eIF 2 and decreased phosphorylation of 4E BP 1 and S6K1 , translation regulators controlled nutritionally by mammalian target of rapamycin . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Moreover , signaling through mTOR , as monitored by the phosphorylation status of eukaryotic initiation factor ( eIF ) 4E binding protein 1 ( 4E BP 1 ) or the 70 kDa ribosomal protein S 6 kinase ( S6K1 ) , was not further enhanced by 10X compared with 1X leucine . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Recently , mice deficient for S 6 Kinase 1 ( S6K1 ) , an effector of the mammalian target of rapamycin ( mTOR ) that acts to integrate nutrient and insulin signals , were shown to be hypoinsulinaemic , glucose intolerant and have reduced beta cell mass . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In cells in culture , the preponderance of evidence suggests that translation of TOP mRNAs is regulated by the mammalian target of rapamycin ( mTOR ) , a protein kinase that signals through ribosomal protein S 6 kinase ( S6K1 ) to rpS 6 . ^^^ However , the results of previous studies were recently challenged by several reports suggesting that translation of TOP mRNAs is independent of mTOR , S6K1 , and S 6 phosphorylation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Incorporation of L [ 1 13C ] leucine in muscle proteins ( fractional synthesis rate , FSR ) was measured in vastus lateralis , before and during a euglycemic hyperinsulinemic hyperaminoacidemic clamp , together with Western blot analysis of protein kinase B ( PKB ) , mTOR , 4E BP 1 , and S6K1 phosphorylation . ^^^ Phosphorylation of PKB , mTOR , and 4E BP 1 were similarly increased by insulin and amino acid in both groups , except for S6K1 phosphorylation , which was not stimulated in elderly subjects . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In mammalian cells , the ribosomal protein S 6 kinases , S6K1 and S6K2 , lie downstream of mTOR and PI3K , suggesting that translational control through the phosphorylation of S 6 regulates cell growth . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In this study , we show that phorbol esters and activated Ras also induce the phosphorylation of tuberin and collaborates with the nutrient sensing pathway to regulate mTOR effectors , such as p 70 ribosomal S 6 kinase 1 ( S6K1 ) . ^^^ RSK 1 phosphorylation of Ser 1798 inhibits the tumor suppressor function of the tuberin / hamartin complex , resulting in increased mTOR signaling to S6K1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Endotoxin disrupts the leucine signaling pathway involving phosphorylation of mTOR , 4E BP 1 , and S6K1 in skeletal muscle . ^^^ LPS also antagonized the Leu induced increase in phosphorylation of S6K1 , ribosomal protein S 6 and mTOR . ^^^ Furthermore , the replacement of plasma insulin like growth factor ( IGF ) 1 in LPS treated rats to basal levels also did not ameliorate the defect in leucine induced phosphorylation of S6K1 or S 6 , although it did reverse the LPS induced decrease in the constitutive phosphorylation of mTOR , S 6 and 4E BP 1 . ^^^ In contrast , to the abovementioned results with leucine , LPS did not prevent the ability of pharmacological levels of IGF 1 to phosphorylate 4E BP 1 , S6K1 , mTOR or alter the availability of eIF4E . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Recent results indicate that an inhibitor of the Ras signaling pathway , farnesylthiosalicylic acid ( FTS ) , decreased phosphorylation of the mTOR effectors , PHAS 1 and S6K1 , in breast cancer cells . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The results show that amino acids enhance signaling through mTOR resulting in phosphorylation of eukaryotic initiation factor 4E binding protein ( 4E BP ) 1 , the 70 kDa ribosomal protein ( rp ) S 6 kinase , S6K1 , and rpS 6 . ^^^ In contrast , glucagon repressed both basal and amino acid induced signaling through mTOR , as assessed by changes in the phosphorylation of 4E BP 1 and S6K1 . ^^^ Thus , glucagon represses phosphorylation of 4E BP 1 and S6K1 through the activation of a protein kinase A LKB AMPK mTOR signaling pathway , while simultaneously enhancing phosphorylation of other downstream effectors of mTOR through the activation of the extracellular signal regulated protein kinase 1 p 90 ( rsk ) signaling pathway . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The phosphorylation of mTOR , S6K1 , the ribosomal protein ( rp ) S 6 , and eIF4G was not altered in hearts from septic rats under basal conditions . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Our studies demonstrated that forskolin generated cAMP resulted in activation of mTOR at basal glucose concentrations as assessed by phosphorylation of S6K1 , a downstream effector of mTOR . ^^^ Glyburide , an inhibitor of ATP sensitive K+ channels ( K ( ATP ) channels ) , provided partial activation of mTOR at basal glucose concentrations due to the influx of extracellular Ca2+ , and diazoxide , an activator of KATP channels , resulted in partial inhibition of S6K1 phosphorylation by 20 mmol / l glucose . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here we chiefly focus on dS6k and S6K1 , whose activities are regulated by an upstream kinase termed the mammalian target of rapamycin ( mTOR , or dTOR in Drosophila ) . ^^^ Our understanding of the mechanisms regulating the mTOR / S6K1 signalling pathway will be fundamental in determining the mechanisms which control cell growth in response to insulin signalling . ^^^ Recent findings from this laboratory and others suggests that the tumour suppressor complex made of two proteins TSC1 / hamartin and TSC2 / tuberin , acts as a negative regulator of mTOR / S6K1 signalling . ^^^ Here we review recent findings demonstrating that the TSC1 / TSC2 inhibitory complex normally acts on Rheb to mediate mTOR / S6K1 signalling . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Insulin rapidly ( t ( 1 / 2 ) = 5 min ) stimulated the mTOR pathway , as reflected by a 10 fold stimulation of 70 kDa ribosomal S 6 kinase 1 ( S6K1 ) activity in 3T3 L 1 adipocytes . ^^^ Inhibition of mTOR / S6K1 by rapamycin increased insulin stimulated glucose transport by as much as 45 % in 3T3 L 1 adipocytes . ^^^ Activation of mTOR / S6K1 by insulin was associated with a rapamycin sensitive increase in Ser636 / 639 phosphorylation of insulin receptor substrate ( IRS ) 1 but , surprisingly , did not result in impaired IRS 1 associated phosphatidylinositol ( PI ) 3 kinase activity . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In this paper we show that basal ( fasting state ) activation of mTOR and its downstream target S6K1 is markedly elevated in liver and skeletal muscle of obese rats fed a high fat diet compared with chow fed , lean controls . ^^^ Time course studies also revealed that mTOR and S6K1 activation by insulin was accelerated in tissues of obese rats , in association with increased inhibitory phosphorylation of insulin receptor substrate 1 ( IRS 1 ) on Ser636 / Ser639 and impaired Akt activation . ^^^ The relationship between mTOR / S6K1 overactivation and impaired insulin signaling to Akt was also examined in hepatic cells in vitro . ^^^ Insulin caused a time dependent activation of mTOR and S6K1 in HepG 2 cells . ^^^ Inhibition of mTOR / S6K1 by rapamycin blunted insulin induced Ser636 / Ser639 phosphorylation of IRS 1 , leading to a rapid ( approximately 5 min ) and persistent increase in IRS 1 associated phosphatidylinositol 3 kinase activity and Akt phosphorylation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
S6K1 , like other serine and threonine kinases activated by insulin ( such as mTOR and PKCzeta ) , has recently been shown to participate in negative feedback mechanisms aimed at terminating insulin signaling through IRS ( insulin receptor substrate ) phosphorylation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Atrophy of S6K1 ( / ) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control . ^^^ Here we show that S 6 kinase 1 ( S6K1 ) , a protein kinase activated by nutrients and insulin like growth factors ( IGFs ) , is essential for the control of muscle cytoplasmic volume by Akt and mTOR . ^^^ Deletion of S6K1 does not affect myoblast cell proliferation but reduces myoblast size to the same extent as that observed with mTOR inhibition by rapamycin . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In contrast , the insulin stimulated phosphorylation of the C terminal site Ser64 / 65 is generally sensitive to rapamycin , as is phosphorylation of another well characterized target for mTOR signaling , S6K1 . ^^^ Although 4E BP 1 and S6K1 bind the mTOR partner , raptor , our data indicate that the outputs from mTOR to 4E BP 1 and S6K1 are distinct . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In this study , we found that a mechanism of ezrin related metastatic behavior is linked to an Akt dependent mammalian target of rapamycin ( mTOR ) / p70 ribosomal protein S 6 kinase ( S6K1 ) / eukaryotic initiation factor 4E binding protein 1 ( 4E BP 1 ) pathway . ^^^ These results suggest that blocking the mTOR / S6K1 / 4E BP 1 pathway may be an appropriate target for strategies to reduce tumor cell metastasis . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Nicotinic activation of Akt increased phosphorylation of multiple downstream substrates of Akt in a time dependent manner , including GSK 3 , FKHR , tuberin , mTOR and S6K1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
S 6 kinase 1 ( S6K1 ) is the best characterized effector of mTOR , and its regulation serves as a model for mTOR signaling . ^^^ Here , we demonstrate that the raptor mTOR complex phosphorylates the rapamycin sensitive forms of S6K1 , while the distinct rictor mTOR complex phosphorylates the rapamycin resistant mutants of S6K1 . ^^^ Phosphorylation of Thr ( 389 ) by rictor mTOR is independent of the TOR signaling motif and depends on removal of the carboxyl terminal domain of S6K1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Likewise , indinavir decreased constitutive phosphorylation of eIF4G and mTOR in muscle , but not S6K1 or the ribosomal protein S 6 . ^^^ In contrast , the ability of a maximally stimulating dose of insulin to increase the phosphorylation of PKB , 4E BP 1 , S6K1 , or mTOR was not altered 20 min after intravenous injection . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Meal feeding augmented the phosphorylation of the downstream effectors of mTOR , namely S6K1 and 4E BP 1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The activity of mammalian target of rapamycin ( mTOR ) is essential for phosphorylation of S6K1 and the treatment malanoma cells with rapamycin , a potent inhibitor of mTOR effectively induced melanogenesis . ^^^ The results obtained here provide possible evidence that PLD 1 exerts a negative regulatory role in the melanogenic process through mTOR / S6K1 signaling . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We show that S 6 kinase 1 ( S6K1 ) , but not Akt , directly phosphorylates mTOR in cell free in vitro system and in cells . ^^^ Expression of a constitutively active , rapamycin and wortmannin resistant S6K1 leads to constitutive phosphorylation of mTOR , whereas knock down of S6K1 using small inhibitory RNA greatly reduces mTOR phosphorylation despite elevated Akt activity . ^^^ Importantly , phosphorylation of mTOR by S6K1 occurs at threonine 2446 / serine 2448 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The protein kinase mammalian target of rapamycin ( mTOR ) is a central regulator of cell proliferation and growth , with the ribosomal subunit S 6 kinase 1 ( S6K1 ) as one of the key downstream signaling effectors . ^^^ Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1 . ^^^ A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently , and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed . ^^^ The mTOR protein level , its catalytic activity , its phosphorylation on Ser 2448 , and the activity of S6K1 were all found increased in IGF 1 stimulated myotubes compared to unstimulated myotubes . ^^^ Using C2C12 cells stably expressing rapamycin resistant forms of mTOR and S6K1 , we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Activation of the potential upstream regulators of 4E BP 1 and S6K1 phosphorylation via PKB and mTOR was also observed . ^^^ Furthermore , the results are consistent with a role for assembly of active eIF4G . eIF4E complex and activation of S6K1 in mediating the stimulation of mRNA translation initiation by IGF 1 through a PKB / mTOR signaling pathway . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Phosphorylation of p 70 ribosomal S 6 kinase 1 ( S6K1 ) , a target of mTOR , was increased by 6 . 9 fold in the heart tissue of myosin immunized rats . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
S6K1 is activated by growth factors such as insulin , and by mammalian target of rapamycin ( mTOR ) , which is itself regulated by amino acids . ^^^ Consistent with this , hVps 34 is also inhibited by activation of the AMP activated kinase , which inhibits mTOR / S6K1 in glucose starved cells . hVps 34 appears to lie upstream of mTOR , as small interfering RNA knock down of hVps 34 inhibits the phosphorylation of another mTOR substrate , eIF4E binding protein 1 ( 4EBP1 ) . ^^^ Our data suggest that hVps 34 is a nutrient regulated lipid kinase that integrates amino acid and glucose inputs to mTOR and S6K1 . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Wortmannin and LY 294002 , two specific inhibitors of phosphatidylinositol 3 kinase ( PI3K ) , blocked both Akt and S6K1 phosphorylation , whereas rapamycin , a specific inhibitor of Akt downstream effector , mammalian target of rapamycin ( mTOR ) , suppressed only S6K1 phosphorylation induced by 15 ( S ) HETE suggesting that this eicosanoid activates the PI3K Akt mTOR S6K1 signaling in HDMVEC . ^^^ S ) hydroxyeicosatetraenoic acid induces angiogenesis via activation of PI3K Akt mTOR S6K1 signaling . ^^^ Pharmacologic inhibition of PI3K Akt mTOR S6K1 signaling completely suppressed 15 ( S ) HETE induced in vivo angiogenesis . ^^^ Together , these results show for the first time that 15 ( S ) HETE stimulates angiogenesis via activation of PI3K Akt mTOR S6K1 signaling . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
However , only the EBV+ / III transformed B cells displayed also activation of the phosphatidylinositol 3 kinase ( PI3K ) / Akt pathway that is considered to be the key activator of mTOR and of the mitogen activated protein kinase / extracellular signal regulated kinase ( ERK ) kinase ( MEK ) / ERK pathway that coactivates one of the immediate targets of mTOR , p 70 S6K1 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We observed that angiogenic stimulation of BM endothelial cells activates mTOR and engages its downstream pathways 4E BP 1 and S6K1 , which are inhibited by the mTOR specific blockers rapamycin and CCI 779 . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
To understand the mechanisms by which thrombin induces vascular smooth muscle cell ( VSMC ) DNA synthesis and motility , we have studied the role of phosphatidylinositol 3 kinase ( PI3K ) Akt mammalian target of rapamycin ( mTOR ) S6K1 signaling . ^^^ Blockade of PI3K Akt mTOR S6K1 signaling by LY 294002 , and rapamycin suppressed both thrombin induced VSMC DNA synthesis and migration . ^^^ Together these observations suggest that thrombin induces both VSMC DNA synthesis and motility via EGFR dependent stimulation of PI3K / Akt signaling targeting in parallel the Fra 1 mediated FGF 2 expression and mTOR S6K1 activation . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Activation of mammalian target of rapamycin , an upstream kinase implicated in phosphorylating both 4E BP 1 and S6K1 , was also observed . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Here we show that a redox sensitive mechanism regulates the phosphorylation of the raptor mTOR effector S6K1 , the interaction between raptor and mTOR , and the kinase activity of the raptor mTOR complex . ^^^ Conversely , the reducing reagent BAL ( British anti Lewisite , also known as 2 , 3 dimercapto 1 propanol ) inhibits S6K1 phosphorylation and stabilizes the interaction of mTOR and raptor to mimic the state of the complex under nutrient deprived conditions . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In the present study , we investigated the possible additional participation of a phosphatidylinositol 3 kinase ( PI3K ) / serine threonine protein kinase B ( Akt ) / mammalian target of rapamycin ( mTOR ) / p70 ribosomal S 6 kinase ( S6K1 ) pathway in this growth response . ^^^ Wortmannin , LY 294002 , and NL 71 101 dose dependently inhibited 5 HT induced SMC proliferation . 5 HT stimulated mTOR phosphorylation and the mTOR inhibitor , rapamycin , blocked activations of S6K1 and S 6 ribosomal protein , and inhibited 5 HT induced SMC proliferation . ^^^ We conclude from these studies that a parallel PI3K and reactive oxygen species dependent Akt / mTOR / S6K1 pathway participates independently from MAPK and Rho / ROCK in the mitogenic effect of 5 HT on pulmonary artery SMCs . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We here show that TRAIL resistance in GBM is a consequence of overexpression of the short isoform of the caspase 8 inhibitor , c FLICE inhibitory protein ( FLIP ( S ) ) , and that FLIP ( S ) expression is in turn translationally enhanced by activation of the Akt mammalian target of rapamycin ( mTOR ) p 70 S6 kinase 1 ( S6K1 ) pathway . ^^^ Conversely , pharmacologic or genetic inhibition of mTOR , or the mTOR target S6K1 , suppresses polyribosomal accumulation of FLIP ( S ) mRNA , FLIP ( S ) protein expression , and TRAIL resistance . ^^^ In archived material from 12 human GBM tumors , PTEN status was a predictor of activation of the Akt mTOR S6K1 pathway and of FLIP ( S ) levels , while in xenografted human GBM , activation status of the PTEN Akt mTOR pathway distinguished the tumors inherently sensitive to TRAIL from those which could be sensitized by the mTOR inhibitor rapamycin . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Recent studies have revealed that the signaling pathways regulating the mammalian target of rapamycin such as Akt and S6K1 are frequently activated in pancreatic cancer . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Phosphorylation of mammalian target of rapamycin ( mTOR ) on Ser ( 2448 ) or Ser ( 2481 ) , an upstream kinase responsible for phosphorylating both S6K1 and 4E BP 1 , was increased at all times during meal feeding , although the extent of phosphorylation was greater at 0 . 5 h after feeding than after 1 h . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We show that mTOR and S6K1 maneuver on and off the eukaryotic initiation factor 3 ( eIF 3 ) translation initiation complex in a signal dependent , choreographed fashion . ^^^ When inactive , S6K1 associates with the eIF 3 complex , while the S6K1 activator mTOR / raptor does not . ^^^ Cell stimulation promotes mTOR / raptor binding to the eIF 3 complex and phosphorylation of S6K1 at its hydrophobic motif . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
We found that the Akt , mTOR and p 70 S6 kinase ( S6K1 ) from the PI3K / mTOR signaling pathway were activated in all of the pancreatic cancer cell lines examined . ^^^ When surgically resected tissue specimens of pancreatic ductal adenocarcinoma were examined , phosphorylation of Akt , mTOR and S6K1 was detected in 50 , 55 and 65 % of the specimens , respectively . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
In the November 18 issue of Cell , discover an unidentified function for the eIF 3 translation initiation factor as a scaffold for the dynamic associations of many preinitiation complex components , including the growth regulating kinases mTOR and S6K1 . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Coexpression of cyclin D 1 CDK4 / 6 in cultured cells leads to increased phosphorylation and decreased detection of both TSC 2 and TSC 1 , and promotes the phosphorylation of the mTOR substrates , 4E BP 1 and S6K1 , two key effectors of cell growth that are negatively regulated by the TSC 1 TSC2 complex . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The mammalian target of rapamycin ( mTOR ) regulates nutrient dependent cell growth and proliferation through cytoplasmic targets , such as S 6 kinase 1 ( S6K1 ) . ^^^ However , previously we have found that mTOR shuttles between the nucleus and cytoplasm , and we have proposed that the nucleocytoplasmic shuttling of mTOR is required for the maximal activation of S6K1 . ^^^ Taken together , our observations suggest the existence of a nuclear shuttling signal in mTOR and provide definitive evidence for the requirement of mTOR nuclear import in its cytoplasmic signaling to S6K1 . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
At physiological concentrations ( 2 . 5 microM ) , curcumin rapidly inhibited phosphorylation of the mammalian target of rapamycin ( mTOR ) and its downstream effector molecules , p 70 S6 kinase 1 ( S6K1 ) and eukaryotic initiation factor 4E ( eIF4E ) binding protein 1 ( 4E BP 1 ) , in a panel of cell lines ( Rh 1 , Rh 30 , DU 145 , MCF 7 and Hela ) . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
PGJ 2 + RA treatment inhibited the activity of p 70 ribosomal S 6 kinase 1 ( S6K1 ) , abolishing Zf 9 phosphorylation at serine as did rapamycin [ a mammalian target of rapamycin ( mTOR ) inhibitor ] . ^^^ PGJ 2 + RA induced phosphatase and tensin homolog deleted on chromosome 10 ( PTEN ) , whose overexpression repressed the TGFbeta 1 gene through S6K1 inhibition , decreasing extracellular signal regulated kinase 1 / 2 90 kDa ribosomal S 6 kinase 1 and Akt mTOR phosphorylations . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Rapid rises in plasma insulin and Leu , along with mTOR signaling ( phosphorylation of eIF4G , S6K1 , rpS 6 , and 4E BP 1 ) in adipose tissue were observed during the 3 h meal and declined thereafter . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Two downstream effectors of mammalian TOR , the translational components S6K1 and 4EBP1 , are commonly used as reporters of mTOR activity . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Lipid infusion did not significantly alter either the total amount or phosphorylation state of mTOR , TSC 2 , S6K1 , or the ribosomal protein S 6 under basal conditions . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
S6K1 dephosphorylation may thus be mTOR independent , and the functional mTOR / S6K2 pathway may maintain S 6 phosphorylation . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Hypertrophy of Pten deficient neurons required the activity of the serine threonine kinase mTor . mTor is a master regulator of cell and organ growth which can trigger a cascade of downstream signaling pathways involving , in part , components of the translational machinery , including S6k1 and its substrate the ribosomal protein S 6 . ^^^ The hypertrophic Pten / S6k1 deficient neurons contained high levels of phosphorylated S 6 , similar to Pten deficient neurons , suggesting that the mTor / S6k / S6 branch of the pathway was still active . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Blockade of the mammalian targets of rapamycin ( mTOR ) / 70 kDa ribosomal S 6 kinase 1 ( S6K1 ) pathway by the specific inhibitor rapamycin greatly enhanced M . tbc induced IL 12 / IL 23 p 40 ( p 40 ) and IL 23 p 19 ( p 19 ) mRNA and IL 23 protein expression . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
RNA interference mediated knockdown of TSC 2 , p 70 S6 kinase ( S6K1 ) , raptor , or rictor demonstrates that mTOR regulates mitochondrial activity independently of its previously identified cellular targets . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The activity of mammalian target of rapamycin ( mTOR ) is essential for phosphorylation of S6K1 and the treatment of dermal fibroblasts with rapamycin , a potent inhibitor of mTOR abolished procollagen 1 production . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
Phosphorylation of mammalian target of rapamycin ( mTOR ) on Ser ( 2448 ) or Ser ( 2481 ) or 70 kDa ribosomal protein S 6 kinase ( S6K1 ) on Thr ( 389 ) was not affected by meal feeding or following removal of food . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
These data suggest that p70 / S6K and possibly other targets of mTOR contribute significantly to tumor development and that inhibition of these proteins may be therapeutic for cancer patients with deranged PI3K signaling . . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
The IRS 1 , PIK3R1 , PIK3R2 , AKT 2 , AKT 3 , FRAP 1 , and RPS6KB1 genes were neither amplified nor overexpressed in any of the tumors . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
PD 98059 ( inhibitor of MAP2K1 , also known as MEK 1 , upstream of extracellular signal regulated protein kinases MAPK3 / 1 , also known as ERK1 / 2 ) , wortmannin ( inhibitor of PIK3C2A , also known as PI3K ) , and rapamycin ( inhibitor of FRAP 1 , also known as mTOR , upstream of RPS6KB1 ) each significantly decreased insulin and oxidative stress induced proliferation of theca interstitial cells . ^^^
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA
Interacting proteins: P23443 and P42345	Pubmed	SVM Score :0.0
NA