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phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach
reading

RPS6KB1 phosphorylates IRS1. 10 / 133
| 2 2 58 64
reach
"Both leucine and insulin stimulate mTORC1, resulting in downstream activation of the p70S6K that is thought to phosphorylate insulin receptor substrate 1 (IRS-1) and reduce insulin sensitivity."
reach
"However, suppression of S6K1 activity by mTOR inhibitors can prevent the phosphorylation of insulin receptor substrate 1 (IRS-1), thereby stabilizing IRS-1 and increasing IGF-IR and PI3K signaling to Akt [XREF_BIBR]."
sparser
"Whereas mTORC2 directly phosphorylates AKT, activated p70S6K phosphorylates and negatively regulates insulin receptor substrate 1. xref As insulin receptor substrate 1 is an important upstream activator of PI3K–AKT, phosphorylation of p70S6K, thus, evokes a physiological negative feedback loop toward AKT. xref Phosphorylation of AKT at Ser 473 was slightly attenuated in 3T3 cells expressing active mTOR mutants compared with that in those expressing the wild‐type protein (Fig. xref a), consistent with a previous observation. xref "
sparser
"Activation of mTORC1 can inhibit the PI3K/AKT pathway through a negative feedback loop mediated by p70S6K phosphorylation of insulin receptor substrate 1 ( xref ; xref )."
sparser
"P7170 induced upregulation of IRS-1 levels, which occurs as a result of inhibition of p70S6K-induced phosphorylation of IRS-1 that, in turn, slows IRS-1 degradation (reviewed in ref. [ xref ])."
sparser
"Akt mediated activation of mTOR results in activation of p70S6K, which phosphorylates IRS-1 resulting in inhibition of IRS1."
reach
"This distinctive profile reflects the relief of a feedback loop where active S6K1 directly phosphorylates IRS1, resulting in the degradation of IRS1 and subsequent reduction of growth factor signaling from RTKs to downstream effectors such as AKT 1."
sparser
"The results show that only in IRS-1 108–516 in which serines 302, 307, and 310 are mutated ( xref A, site 2) is IRS-1 not phosphorylated in vitro by S6K1 ( xref C, left panels)."
reach
"Akt mediated activation of mTOR results in activation of p70S6K, which phosphorylates IRS-1 resulting in inhibition of IRS1."
sparser
"As shown in xref , p-S6K1 (T389) was increased in LKB1-deficient WAT whereas the levels of p-IRS1 (Ser636/639) in WAT from LKB1 −/− were reduced when compared with WT, suggesting that increased Akt inhibition in LKB1-deficient WAT was not due to increased phosphorylation of IRS1 by S6K1."
RPS6KB1 phosphorylates IRS1 on serine. 10 / 40
| 3 9 28
reach
"S6K1 knockout mice are protected against obesity and insulin resistance due to elevated energy expenditure and the loss of IRS1 serine phosphorylation by S6K1 [XREF_BIBR, XREF_BIBR]."
reach
"This is due to the fact that many inhibitors lead to irreversible degradation of a protein; An example would be the serine/threonine phosphorylation of the insulin receptor substrate-1 (IRS-1) by S6K1, among other serine kinases, which leads to ubiquitylation and degradation of IRS-1."
sparser
"Under some conditions, p70S6K can also phosphorylate multiple serine residues of insulin receptor substrate-1 (IRS-1) as well as the serine phosphorylate rictor (a component of the mTORC2 complex that activates Akt)."
reach
"A negative feedback regulation is provided by S6K1 which increases an inhibitory serine phosphorylation of IRS-1, leading to downregulation of insulin signaling [XREF_BIBR]."
reach
"However, the activation of mTOR leads to the activation of S6 protein kinase 1 (S6K1), which increases the phosphorylation of serine on IRS-1, creating a negative feedback loop by inhibiting IRS-1 and thus halting insulin 's signaling."
reach
"XREF_BIBR - XREF_BIBR In addition, adiponectin has been shown to increase muscle insulin signaling by reducing p70 S6 kinase mediated serine phosphorylation of insulin receptor substrate 1."
reach
"S6K1 phosphorylates inhibitory serine sites of IRS-1 leading to its degradation, whereas rapamycin prevents inhibitory IRS-1 phosphorylation, stabilizing IRS-1 and induces Akt activity by augmenting IGF-IR signaling to PI3K and Akt."
sparser
"For example, activated S6K1 phosphorylates IRS1 on multiple serine residues. xref The serine - phosphorylated form of IRS1 is known to attenuate the signal from IGF1R to PI3K through inhibition of tyrosine phosphorylation of IRS1 and/or inhibition of tertiary complex formation including IGF1R, PI3K, and IRS1. xref , xref , xref In the present study, the level of the serine-phosphorylated form of IRS1 was significantly decreased within 3 h of exposure to ZSTK474 in all four cell lines examined, suggesting relief from the negative feedback program."
rlimsp
"Using two cell culture models of the familial hamartoma syndrome, tuberous sclerosis, we show here that Raptor-mTOR and S6K1 are required for phosphorylation of IRS1 at a subset of serine residues frequently associated with insulin resistance, including S307, S312, S527, S616, and S636 (of human IRS1)."
reach
"A previous study demonstrated that increased activation of mTOR and S6 kinase beta-1 (S6K1) may promote serine phosphorylation of IRS-1, thus resulting in the pathogenesis of hepatic insulin resistance in obese rats."
RPS6KB1 phosphorylates IRS1 on S307. 10 / 37
1 1 1 | 8 12 14
rlimsp
"This led to phosphorylation of IRS-1 by S6K1 at multiple serine residues including Ser-270, Ser-307, Ser-636, and Ser-1101 in human IRS-1 (Ser-265, Ser-302, Ser-632, and Ser-1097, in rodent IRS-1)."
sparser
"The insulin- and nutrient-stimulated kinase S6k1 phosphorylates Irs1 at Ser302, as well as other putatively inhibitory sites ( xref )."
reach
"First, it was found that S6K1 and S6K2 phosphorylate IRS-1 on serine 302, a site adjacent to its PTB domain."
rlimsp
"p70S6K phosphorylates IRS-1 in serine 307 which leads to the uncoupling between IRS-1 and p85 (the regulatory subunit of PI3K) and therefore causing the lack of response of HepG2 to IGF-1."
sparser
"We did not observe elevated levels of components of mTOR/S6K pathway in case of single Pten or Lkb1 deletion in the bladder, however we show that Lkb1 deletion led to increased Ser302 phosphorylation of IRS-1 (equivalent to human Ser307 residue) by p70S6K ( xref )."
reach
"The mTORC1-downstream p70 ribosomal protein S6 kinase (S6K1), which is activated by insulin, can phosphorylate IRS1 at serine 307 in vitro and is considered the physiological protein kinase."
rlimsp
"S6K1 was found to phosphorylate a large fragment of IRS1 at Ser307 in vitro, and insulin-induced phosphorylation was blocked by knock-down of S6K1 in TSC2−/− mouse embryo fibroblasts [36]."
sparser
"p70S6K phosphorylates IRS-1 in serine 307 which leads to the uncoupling between IRS-1 and p85 (the regulatory subunit of PI3K) and therefore causing the lack of response of HepG2 to IGF-1."
biopax:netpath
No evidence text available
rlimsp
"A point mutant of IRS-1 (S270A) impaired association of IRS-1 with S6K1 resulting in diminished phosphorylation of IRS-1 at three other S6K1 phosphorylation sites (Ser-307, Ser-636, and Ser-1101)."
RPS6KB1 phosphorylates IRS1 on S1101. 10 / 16
1 1 1 | 2 4 7
signor
"Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulates insulin."
biopax:phosphositeplus
No evidence text available
reach
"Ribosomal protein S6 kinase beta-1 (S6K1) phosphorylation of insulin receptor substrate 1 (IRS-1) at S1101 blocks its interaction with PI3K, leading to insulin resistance."
reach
"S6K1 phosphorylates insulin receptor substrate 1 (IRS-1) at Ser1101 and Ser302."
reach
"In addition, S6K1 phosphorylates IRS-1 at Ser 1101 and suppresses IGF-1 receptor mediated activation of the PI3K pathway XREF_BIBR."
reach
"Here we show that S6K1 directly phosphorylates IRS-1 Ser 1101 in vitro in the C-terminal domain of the protein and that mutation of this site largely blocks the ability of amino acids to suppress IRS-1 tyrosine and Akt phosphorylation."
sparser
"S6K1 phosphorylates IRS-1 at Ser-1101 and suppresses PI3K activation."
sparser
"Infusion of amino acids into humans leads to the activation of S6K1 phosphorylation of IRS-1 Ser 1101 , a reduction of IRS-1 function and insulin resistance in skeletal muscle [ xref ]."
reach
"Infusion of amino acids into humans leads to the activation of S6K1 phosphorylation of IRS-1 Ser 1101, a reduction of IRS-1 function and insulin resistance in skeletal muscle [XREF_BIBR]."
biopax:netpath
No evidence text available
RPS6KB1 phosphorylates IRS1 on S636. 8 / 8
1 1 2 | 1 3
reach
"p70S6K phosphorylates IRS-1 on S312 and/or S636 and S639."
reach
"p70S6K can phosphorylate IRS-1 on S312 and/or S636 and S639."
biopax:netpath
No evidence text available
signor
"Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulatesinsulin."
biopax:phosphositeplus
No evidence text available
signor
"In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8"
reach
"IRS-1 is phosphorylated at Ser636 by S6K1 which is activated by mTOR."
sparser
"IRS-1 S302 and S632 (S307 and S636, respectively, in humans) are directly phosphorylated by S6K1 and mTORC1, respectively ( Copps and White, 2012 )."
RPS6KB1 phosphorylates IRS1 on S312. 8 / 8
| 3 5
reach
"At low levels, amino acids increase Akt phosphorylation in isolated muscle cells and improve insulin sensitivity, but at higher concentrations amino acids strongly activate p70 S6 kinase 1 which directly phosphorylates IRS1 on inhibitory serine residues 312 and 636/639 and blunts Akt phosphorylation."
reach
"p70S6K can phosphorylate IRS-1 on S312 and/or S636 and S639."
reach
"IRS-1 is phosphorylated by S6K1 at Ser312 resulting in its dissociation from the IGF-1 receptor, and proteasome mediated degradation (Shi et al, 2005)."
sparser
"p70S6K can phosphorylate IRS-1 on S312 and/or S636/S639."
reach
"p70S6K phosphorylates IRS-1 on S312 and/or S636 and S639."
sparser
"p70S6K phosphorylates IRS-1 on S312 and/or S636/S639."
reach
"When alternative IRS-1 sites, S307 and S312 are phosphorylated by S6K1, it enhances proteasomal degradation, also leading to insulin resistance."
sparser
"IRS-1 is phosphorylated by S6K1 at Ser312 resulting in its dissociation from the IGF-1 receptor, and proteasome-mediated degradation ( xref )."
RPS6KB1 phosphorylated on T412, S441, T252, S394, S447, S434, and T444 phosphorylates IRS1 phosphorylated on S270 on S636. 5 / 5
5 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RPS6KB1 phosphorylates IRS1 on S639. 5 / 5
2 | 3
reach
"p70S6K phosphorylates IRS-1 on S312 and/or S636 and S639."
signor
"In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8"
reach
"p70S6K can phosphorylate IRS-1 on S312 and/or S636 and S639."
reach
"mTOR and its downstream effector S6K1 suppress IRS1 activity by directly phosphorylating IRS1 at Ser636 and Ser639 and Ser307, respectively, which leads to desensitization of insulin signaling."
signor
"Nevertheless, s6k1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from s6k1 to insulin receptor substrate 1 (irs1), which blunts s307 and s636/s639 phosphorylation; thus under conditions of nutrient satiation s6k1 negatively regulatesinsulin."
RPS6KB1 phosphorylated on T412, S441, T252, S394, S447, S434, and T444 phosphorylates IRS1 phosphorylated on S270 on S1101. 5 / 5
5 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RPS6KB1 phosphorylated on T412, S441, T252, S394, S447, S434, and T444 phosphorylates IRS1 phosphorylated on S270 on S307. 5 / 5
5 |
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
biopax:pid
No evidence text available
RPS6KB1-S6K phosphorylates IRS1. 4 / 4
| 4
reach
"p70 S6K also phosphorylates and inhibits insulin receptor substrate-1 (IRS-1), forms a negative feed back regulation of PI3K and Akt signaling."
reach
"Importantly, p70 S6K phosphorylates and inhibits IRS-1, resulting in a negative feed back to Akt and mTOR signaling."
reach
"We show that in skeletal muscle, adiponectin promotes tyrosine phosphorylation of IRS1 and AKT phosphorylation via inhibiting p70 S6K phosphorylation and serine phosphorylation of IRS1, thereby increasing insulin sensitivity."
reach
"ERK, not MTOR and p70 S6K, mediates the phosphorylation of IRS1 in the liver extracts."
RPS6KB1 phosphorylates IRS1 on S270. 3 / 3
1 1 1 |
signor
"Turnover of the active fraction of irs1 involves raptor-mtor- and s6k1-dependent serine phosphorylation in cell culture models of tuberous sclerosiss6k1 phosphorylates irs1 in vitro on multiple residues showing strong preference for rxrxxs/t over s/t,p sites."
biopax:phosphositeplus
No evidence text available
biopax:netpath
No evidence text available
RPS6KB1 phosphorylates IRS1 on S527. 3 / 3
1 2 |
biopax:phosphositeplus
No evidence text available
signor
"In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8"
signor
"Turnover of the active fraction of irs1 involves raptor-mtor- and s6k1-dependent serine phosphorylation in cell culture models of tuberous sclerosiss6k1 phosphorylates irs1 in vitro on multiple residues showing strong preference for rxrxxs/t over s/t,p sites."
Kinase-active RPS6KB1 leads to the phosphorylation of IRS1. 1 / 1
1 |
bel
"S6K was shown to directly phosphorylate IRS-1 to inhibit phosphatidylinositol-3-kinase (PI3K) and Akt activation (Harrington ete al, 2004)."
RPS6KB1-S6K phosphorylates IRS1 on serine. 1 / 1
| 1
reach
"A number of works showed that p70 S6K, which is downstream of mTOR, could phosphorylate serine residues on IRS-1 to result in proteasomal degradation."
RPS6KB1 phosphorylated on T412, S441, T252, S394, S447, S434, and T444 phosphorylates IRS1 on S270. 1 / 1
1 |
biopax:pid
No evidence text available