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UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining

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EIF4EBP1 — INS

Text-mined interactions from Literome

Pham et al., Circ Res 2000 : 4E-BP1 was phosphorylated in unstimulated cells, and 4E-BP1 phosphorylation was increased by insulin ... The effects of H ( 2 ) O ( 2 ) were sufficient to override the stimulation of protein synthesis and 4E-BP1 phosphorylation induced by insulin
Lin et al., Diabetologia 1997 : When PHAS-I is phosphorylated in response to insulin , the PHAS-I/eukaryotic initiation factor-4E complex dissociates ... These results suggest that the phosphorylation of PHAS-I in response to insulin occurs via the p70S6K signalling pathway
Maeurer et al., Cell Signal 2009 : Increased intracellular PAM concentrations facilitated S1P- and insulin induced mTOR activation as well as p70S6K and 4EBP1 phosphorylation while genetic deletion of PAM decreased S1P- and insulin induced mTOR activation
O'Connor et al., Am J Physiol Endocrinol Metab 2004 : Amino acids and insulin increased protein S6 kinase and 4E-binding protein 1 (4E-BP1) phosphorylation ; however, only amino acids decreased formation of the inactive 4E-BPI.eukaryotic initiation factor-4E (eIF4E) complex
Herbert et al., J Biol Chem 2000 : Stimulation of serum starved human embryonic kidney (HEK) 293 cells with either the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate ( TPA ), or insulin resulted in increases in the phosphorylation of 4E-BP1 and p70 S6 kinase, eIF4F assembly, and protein synthesis
Chotechuang et al., Am J Physiol Endocrinol Metab 2009 : Either AAs or insulin can stimulate p-mTOR, but this is not sufficient for 4E-BP1 phosphorylation that requires both ( P < 0.01 ) ... As expected, branched-chain AAs ( BCAA ) or leucine stimulated the phosphorylation of mTOR, but both insulin and BCAA or leucine are required for 4E-BP1 phosphorylation
Shen et al., Pediatr Res 2005 : The insulin induced increase in 4E-BP1 phosphorylation was more pronounced, and the gamma percentage was 56 % on average in the insulin group ... The insulin induced increase in 4E-BP1 phosphorylation was lower than in fed animals and did not result in significant changes in eIF4E.4E-BP1 binding or eIF4E.eIF4G binding ... This reduced insulin induced 4E-BP1 phosphorylation was not due to a global defect in insulin signaling ; the defects underlying the reduced basal phosphorylation and insulin-responsiveness of 4E-BP1 in fasted animals may be in signaling components other than, or downstream of, PKB/Akt
Wu et al., Endocrinology 2004 : Insulin enhanced the phosphorylation of Akt ( P < 0.04 ), 4E-BP1 ( P < 0.002 ), and p70 ( S6K ) ( P < 0.0001 ) in ADX, but not in sham rats ... Dexamethasone restored the levels of 4E-BP1 and p70 ( S6K ) phosphorylation and abrogated the insulin stimulated Akt, 4E-BP1 , and p70 ( S6K ) phosphorylation
Guillet et al., FASEB J 2004 : Phosphorylation of PKB, mTOR, and 4E-BP1 were similarly increased by insulin and amino acid in both groups, except for S6K1 phosphorylation, which was not stimulated in elderly subjects
Beugnet et al., Biochem J 2003 : We show in the present study that inhibition of protein synthesis by any of several protein synthesis inhibitors tested allows insulin to regulate 4E-BP1 or S6K1 in amino-acid deprived cells, as does the addition of amino acids to the medium
Azpiazu et al., J Biol Chem 1996 : Regulation of both glycogen synthase and PHAS-I by insulin in rat skeletal muscle involves mitogen activated protein kinase independent and rapamycin-sensitive pathways ... Insulin also increased the phosphorylation of PHAS-I ( phosphorylated heat- and acid-stable protein ) and promoted the dissociation of the PHAS-I*eIF-4E complex ... Increasing MAP kinase activity with EGF did not mimic the effect of insulin on PHAS-I phosphorylation, and the effect of insulin on increasing MAP kinase could be abolished with the MEK inhibitor without decreasing the effect of insulin on PHAS-I ... The effects of insulin on PHAS-I were attenuated by rapamycin
Terruzzi et al., Acta Diabetol 2005 : Differential p70S6k and 4E-BP1 regulation by insulin and amino acids in vascular endothelial and smooth muscle cells ... INS stimulated p70S6k and 4E-BP1 phosphorylation transiently in HUVEC and persistently in HVSMC ... AA and INS+AA stimulated p70S6k and 4E-BP1 phosphorylation persistently in HUVEC and HVSMC
Palaniappan et al., Mol Cell Endocrinol 2013 : Pharmacological inhibition of MTORC1 with rapamycin abrogated the insulin induced phosphorylation of EIF4EBP1 , RPS6KB1 and its downstream effector, RPS6
Long et al., Am J Physiol Endocrinol Metab 2003 : Insulin significantly enhanced the phosphorylation of Akt ( P < 0.03 ), 4E-BP1 ( P = 0.003 ), and p70 ( S6K ) ( P < 0.002 ) in ADX but not in Sham rats ... Glucocorticoid replacement blunted the effect of insulin on Akt, 4E-BP1 , and p70 ( S6K ) phosphorylation and protein synthesis
Cao et al., Science signaling 2009 : Loss of Galpha ( i1 ) and Galpha ( i3 ) severely impaired the activation of Akt and of p70 S6 kinase and 4E-BP1 , downstream targets of mTORC1, in response to EGF, heparin binding EGF-like growth factor, and transforming growth factor alpha, but not insulin , insulin-like growth factor, or platelet derived growth factor
Mèndez et al., Mol Cell Biol 1996 : Stimulation of protein synthesis, eukaryotic translation initiation factor 4E phosphorylation, and PHAS-I phosphorylation by insulin requires insulin receptor substrate 1 and phosphatidylinositol 3-kinase
Iynedjian et al., Biochem J 2000 : These effects were comparable to the insulin induced activation of endogenous PKB and phosphorylation of PHAS-I in non transduced hepatocytes
Galbaugh et al., BMC cell biology 2006 : The activation of p70S6K by insulin or EGF resulted in the phosphorylation of ribosomal protein S6 (RPS6), elongation initiation factor 4E ( elF4E ) and 4E binding protein1 (4E-BP1) ... But lower levels of PI-3-K and mTOR inhibitors were required to block insulin induced phosphorylation of RPS6 than EGF induced phosphorylation, and insulin induced phosphorylation of elF4E and 4E-BP1 was not completely mTOR dependent suggesting some diversity of signaling for EGF and insulin
Scott et al., J Biol Chem 1998 : Incubating 3T3-L1 adipocytes with forskolin, which increases intracellular cAMP by activating adenylate cyclase, mimicked rapamycin by attenuating the effect of insulin on stimulating the phosphorylation of four ( S/T ) P sites in PHAS-I , a downstream target of the mammalian target of rapamycin (mTOR) signaling pathway ... These findings support the interpretation that increasing cAMP attenuates the effects of insulin on PHAS-I , p70 ( S6K ), and other downstream targets of the mTOR signaling pathway by inhibiting the phosphorylation and activation of mTOR
Wang et al., Am J Physiol Heart Circ Physiol 2000 : Insulin caused phosphorylation of 4E-BP1 and induced its dissociation from eIF4E, and these effects were also blocked by rapamycin
Campbell et al., Biochem J 1999 : These results add substantially to the emerging evidence that nutrients themselves modulate functions of mammalian cells and indicate that ( i ) nutrients modulate the activation of eIF2B and eEF2 through as-yet unidentified mechanisms and ( ii ) regulation of p70 S6 kinase and 4E-BP1 by insulin requires other inputs in addition to protein kinase B
Ramírez-Rangel et al., Mol Cell Biol 2011 : GRp58/ERp57 knockdown reduces mTORC1 levels and phosphorylation of 4E-BP1 and p70 ( S6K ) in response to insulin
El-Chaâr et al., International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 2004 : Insulin stimulated 4E-BP1 phosphorylation in 3T3-L1 preadipocytes was only partially affected by rapamycin, consistent with the differentiation data
Suryawan et al., Am J Physiol Endocrinol Metab 2007 : Both INS and AA increased protein synthesis and the phosphorylation of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase-1, and eukaryotic initiation factor (eIF)4E binding protein 1 ( 4E-BP1 ), and these responses were higher in 6-day-old compared with 26-day-old pigs
Deshmukh et al., Mol Endocrinol 2008 : Insulin stimulation increased phosphorylation of S6K1 ( Thr389 ), ribosomal protein S6 ( Ser235/236 ), and 4E-BP1 ( Thr37/46 ) ( P < 0.01 ) in WT, AMPK alpha2 KO, and AMPK gamma3 KO mice
Kimball et al., Am J Physiol 1998 : Insulin also stimulated phosphorylation of 4E-BP1 as well as dissociation of the 4E-BP1.eIF-4E complex ... Both rapamycin and wortmannin completely blocked the insulin induced changes in 4E-BP1 phosphorylation and association of 4E-BP1 and eIF-4E ; PD-98059 had no effect on either parameter
Lai et al., Biochem J 2012 : Incubation with high doses of MK-2206 ( 10 µM ) inhibited insulin induced p70 ribosomal protein S6 kinase and 4E-BP1 ( eukaryotic initiation factor 4E-binding protein-1 ) phosphorylation associated with increased eEF2 ( eukaryotic elongation factor 2 ) phosphorylation
Hara et al., J Biol Chem 1997 : The proteins eIF-4E BP1 and p70 S6 kinase each undergo an insulin/mitogen stimulated phosphorylation in situ that is partially inhibited by rapamycin
Liu et al., J Biol Chem 2010 : Treating C2C12 cells with RSV dramatically inhibited insulin stimulated Akt, S6 kinase, and 4E-BP1 phosphorylation but had little effect on tyrosine phosphorylation of the insulin receptor and activation of the p44/42 MAPK signaling pathway
Oleksiewicz et al., J Appl Toxicol 2011 : By western blotting with phospho-specific antibodies, insulin induced phosphorylation of IRS-1, Akt, p70S6K, S6 ribosomal protein, 4E-BP1 , FoxO3a, FoxO1, p44/42 MAPK and the EGFR
Patel et al., Biochem J 2001 : Insulin and other agents induce the phosphorylation of 4E-BP1 at multiple sites, resulting in its release from eIF4E, and this involves signalling through the mammalian target of rapamycin (mTOR)
Yang et al., Nat Cell Biol 2000 (Ataxia Telangiectasia...) : Here we report that ATM, the protein product of the ATM gene that is mutated in the disease ataxia telangiectasia, phosphorylates 4E-BP1 at Ser 111 in vitro and that insulin treatment induces phosphorylation of 4E-BP1 at Ser 111 in vivo in an ATM dependent manner
Fonseca et al., J Biol Chem 2007 : Small interfering RNA mediated knockdown of PRAS40 impairs both the amino acid- and insulin stimulated phosphorylation of 4E-BP1 and the phosphorylation of S6
Long et al., Am J Physiol Endocrinol Metab 2000 (Body Weight) : We examined whether phosphorylation of PHAS-I and p70 ( S6k ) was increased by feeding and determined the separate effects of insulin and amino acids on PHAS-I and p70 ( S6k ) phosphorylation in rat skeletal muscle in vivo
Lin et al., J Biol Chem 1995 : Insulin increased PHAS-I protein ( 3.3-fold after 2 days ), the rate of PHAS-I synthesis ( 3-fold after 1 h ), and the half-life of the protein ( from 1.5 to 2.5 days ) ... Insulin also increased the phosphorylation of PHAS-I and promoted dissociation of the PHAS-I eukaryotic initiation factor-4E (eIF-4E) complex, effects that were maximal within 10 min ... In summary, insulin increases the expression of PHAS-I and promotes phosphorylation of multiple sites in the protein via multiple transduction pathways, one of which is rapamycin-sensitive and independent of MAP kinase
Xu et al., J Biol Chem 1998 : Insulin mediates glucose stimulated phosphorylation of PHAS-I by pancreatic beta cells ... Our initial approach was to determine if this effect is mediated by the metabolism of glucose and activation of islet cell protein kinases, or whether insulin secreted from the beta cell stimulates phosphorylation of PHAS-I via an insulin-receptor mechanism as described for insulin-sensitive cells ... Studies with beta cell lines and islets indicate that amino acids are required for glucose or exogenous insulin to stimulate the phosphorylation of PHAS-I, and amino acids alone dose-dependently stimulate the phosphorylation of PHAS-I , which is further enhanced by insulin
Takata et al., J Biol Chem 1999 : Insulin induced phosphorylation of 4E-BP1 was inhibited by Akt-AA in Chinese hamster ovary cells ... However, lambdaDeltaNKD had no effect on 4E-BP1 phosphorylation induced by insulin ... These data suggest that Akt, but not PKClambda, is required for insulin activation of glycogen synthase and for insulin induced phosphorylation of 4E-BP1
Wang et al., J Biol Chem 2006 : Insulin stimulates protein synthesis by promoting phosphorylation of the eIF4E binding protein, 4EBP1 ... The stimulatory effects of insulin on both 4EBP1 kinase activity and binding occurred rapidly and at physiological concentrations of insulin, and both effects required an intact mTORC1
Diggle et al., Biochem J 1996 : This study compares the effects of insulin and epidermal growth factor (EGF) on the phosphorylation of 4E-BP1 in fat-cells ( followed by gel-shift assays and incorporation of 32P ) and on its association with eIF-4E ... It is concluded that in rat epididymal fat-cells, the effects of insulin on 4E-BP1 involves multiple phosphorylation events
Kimball et al., Am J Physiol 1996 (Diabetes Mellitus, Experimental) : The effects of both insulin and diabetes on PHAS-I binding to eIF-4E appeared to be due to changes in PHAS-I phosphorylation ... The results indicate that the effects of both insulin and diabetes on protein synthesis in skeletal muscle involve modulation of the interaction of PHAS-I and eIF-4E
Heesom et al., Biochem J 1998 : The effects of insulin and rapamycin on the phosphorylation of the translation regulator, initiation factor 4E-binding protein 1 (4E-BP1) have been studied in rat fat cells by following changes in the incorporation of 32P from [ 32P ] Pi under steady-state conditions ... However, the present study also provides evidence that insulin increases the phosphorylation of 4E-BP1 bound to eIF4E on a further site ( Ser-111 ) and that this is by a rapamycin-insensitive mechanism
Mariappan et al., Diabetes 2007 : High glucose, high insulin , and high glucose+high insulin stimulated phosphorylation of 4E-BP1 , a repressor binding protein for eukaryotic initiation factor 4E (eIF4E), that was dependent on activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin
Brautigan et al., Biochem Biophys Res Commun 2006 : Phosphorylation of MAPK or 4E-BP1 as markers for insulin signaling is stimulated by vanadate plus insulin , and chromium does not enhance the effects
von Manteuffel et al., Proc Natl Acad Sci U S A 1996 : More striking, insulin , which does not induce p42mapk activation in human 293 cells or Swiss mouse 3T3 cells, induces 4E-BP1 phosphorylation and p70s6k activation in both cell types ... The insulin effect on 4E-BP1 phosphorylation and p70s6k activation in both cell types is blocked by SQ20006, wortmannin, and rapamycin
Miranda et al., Pflugers Arch 2008 : Insulin , on the other hand, stimulated protein synthesis ( by 30 % ) and increased p70 ribosomal protein S6 kinase (p70S6K) Thr389, 40S ribosomal protein S6 ( rpS6 ) Ser235/236, rpS6 Ser240/244 and eukaryotic initiation factor-4E binding protein-1 (4E-BP1) Thr37/46 phosphorylation over basal values
Wang et al., Cell Microbiol 2009 : Infected cells still phosphorylated S6K1 and 4E-BP1 in response to insulin , although the S6K1 response was blunted
Long et al., Am J Physiol Endocrinol Metab 2001 : DEX did not affect basal PHAS-I or p70 ( S6k ) phosphorylation but blocked insulin stimulated phosphorylation of PHAS-I- and amino acid stimulated phosphorylation of both PHAS-I and p70 ( S6k ) ( P < 0.01, for each )
Tee et al., Mol Cell Biol 2002 : 4E-BP1 undergoes insulin stimulated phosphorylation, resulting in its release from eIF4E, allowing initiation complex assembly
Wilson et al., Am J Physiol Endocrinol Metab 2008 : Furthermore, insulin reduced inactive 4E-BP1.eIF4E complex association and increased active eIF4E.eIF4G complex formation, indicating enhanced eIF4F complex assembly
Williamson et al., Am J Physiol Endocrinol Metab 2005 : INS also promoted phosphorylation of ERK1/2, S6K1, and 4E-BP1 and dephosphorylation of eIF4E
Zhang et al., Free Radic Biol Med 2009 : Insulin also increased 4E-BP1 coprecipitating with mTOR and the phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1
Lee et al., J Biol Chem 2005 : We also show that insulin stimulated the phosphorylation of 4E-binding protein 1 (4E-BP1) and p70S6 kinase (p70S6K) in a mTOR dependent manner
Bhandari et al., Kidney Int 2001 : Insulin regulation of protein translation repressor 4E-BP1 , an eIF4E binding protein, in renal epithelial cells ... We examined insulin regulation of 4E-BP1 phosphorylation in murine proximal tubular epithelial cells ... Insulin also augmented 4E-BP1 phosphorylation and phosphatidylinositol 3-kinase ( PI 3-kinase ) activity in antiphosphotyrosine immunoprecipitates ... Rapamycin abrogated 4E-BP1 phosphorylation in response to insulin , suggesting involvement of mammalian target of rapamycin (mTOR), a kinase downstream of Akt ... Insulin stimulated phosphorylation of 4E-BP1 was also inhibited by PD098059, implying involvement of Erk-1/-2 mitogen activated protein ( MAP ) kinase
von Manteuffel et al., Mol Cell Biol 1997 : Employing specific inhibitors and docking-site mutants of growth factor receptors, recent studies have indicated that the insulin induced increase in 40S ribosomal protein S6 and initiation factor 4E binding protein 1 (4E-BP1) phosphorylation is mediated by the mTOR/FRAP-p70s6k signal transduction pathway ... Unexpectedly, the rapamycin-resistant p70s6k inhibited insulin induced 4E-BP1 phosphorylation in a dose dependent manner