IndraLab

Statements

RPS6KB1 phosphorylates IRS1. 10 / 159
| 2 76 72 2
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."
25926513
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 )."
26233890
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 ])."
25491778
reach
"Akt mediated activation of mTOR results in activation of p70S6K, which phosphorylates IRS-1 resulting in inhibition of IRS1."
19690459
reach
"XREF_BIBR - XREF_BIBR mTORC1 then activates S6 kinase 1 (S6K1) which phosphorylates IRS-1 on serines residues and inhibits insulin signaling."
23145367
sparser
"On the other hand, the mTORC1 substrate RPS6KB1 phosphorylates and inhibits IRS1 [ xref , xref ]."
33544134
reach
"Although S6K1 is an effector of growth, recent reports show that amino acids also negatively affect insulin signaling through mTOR and S6K1 phosphorylation of IRS1."
16753575
reach
"mTOR can increase p70S6K, which in turn phosphorylates and inhibits insulin receptor substrate 1, a protein upstream of PI3K and AKT."
25933683
rlimsp
"Although S6K1 is an effector of growth, recent reports show that amino acids also negatively affect insulin signaling through mTOR/S6K1 phosphorylation of IRS1."
16753575
sparser
"The activated S6K1 phosphorylates IRS1 and Rictor in negative feedback loops [ xref ]."
27149630
RPS6KB1 phosphorylates IRS1 on serine. 10 / 48
| 35 10 3
reach
"The results show that targeted pharmacologic interventions with DPP-4 inhibitor could be useful in ameliorating pathophysiologic abnormalities in cardiac diastolic dysfunction and preventing the activation of insulin metabolic signaling molecules through enhanced mTOR/S6K1 activation and Ser phosphorylation of IRS-1 and IRS-2."
30116740
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)."
16914728
reach
"Activation of the cell nutrient sensor mTOR and S6K1 kinase causes serine phosphorylation of IRS-1, with a subsequent decline in the IRS1-associated PI3K activity."
35212998
reach
"It has been proposed that an S6K1 associated negative feedback loop results in the inhibitory serine phosphorylation of IRS1 in response to mTOR activation."
19574345
reach
"It has been reported that inhibition of mTORC1 signaling by rapamycin can abrogate S6K1 activity (Saitoh et al., 2002); we therefore used rapamycin to investigate whether mTORC1 and S6K1 directly part[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25813876
reach
"This is because activated mTORC1 and S6K1 phosphorylates serine residues of IRS-1 (S302, S307, S612, and S1101) (Gual et al., 2005)."
33400857
reach
"In addition, it was reported that rapamycin inhibited mTORC1 and p70 S6 kinase induced serine phosphorylation of IRS-1 and promoted smooth muscle differentiation by potentiating IGF-1-induced Akt2 activation [XREF_BIBR]."
24694942
reach
"Once activated by insulin, mTOR and p70S6K phosphorylates insulin receptor substrate-1 (IRS-1) on serine residues, resulting in its inhibition and reduction of insulin signaling."
21602475
sparser
"P70S6K can also phosphorylate IRS1 on an inhibitory serine residue, thus causing negative feedback that inhibits insulin and IGF signaling to PI3K/AKT ( xref )."
27758884
reach
"The stability of IRS-1 was reduced by serine phosphorylation, and long-term insulin stimulation caused mTORC1 and S6K1 hyperactivation and markedly enhanced insulin induced IRS-1 serine phosphorylatio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25813876
RPS6KB1 phosphorylates IRS1 on S307. 10 / 45
1 1 1 | 20 14 8
reach
"We observed that S6K1-dependent phosphorylation of IRS1 on S307 and S1101 was diminished in SH-SY5Y cells treated with miR-200b and miR-200c.The oAβ leads to additional generation of oAβ resulted from abnormal autophagosome accumulation via inhibition of mTOR pathway [17]."
29738527
rlimsp
"Our findings demonstrate that it is unlikely that S6K1 is the protein kinase that phosphorylates IRS1 at Ser307 in response to insulin stimulation of human adipocytes."
23565163
reach
"The very different dynamics for phosphorylation of IRS1 at Ser307, on one hand, and of S6K1 at threonine 389 and S6 at serine 235/236, on the other, suggest that IRS1 is not phosphorylated at Ser307 by S6K1."
23565163
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). Direct phosphorylation of these sites by S6K1 was observed in an in vitro kinase assay using purified IRS-1 and S6K1."
18952604
reach
"In in vitro kinase assays, S6K1 directly phosphorylates S302 of mouse IRS-1, a site matching its preferred substrate recognition motif."
15533996
reach
"Most likely, mTORC1 itself, rather than S6K1, phosphorylates IRS1 on Ser 307 to effect the inhibition of PI3K-Akt signaling, subsequently suppressing myogenic differentiation."
24068326
reach
"Activation of the mTOR pathway functions as a feedback regulator of insulin action by increasing phosphorylation of IRS1 at Ser307 [pIRS (S307)] and Ser636/639 [pIRS (S636/639)] by S6K1 and mTOR, respectively."
18949383
sparser
"Consistent with these observations it was found that S6K1 and S6K2 phosphorylate IRS-1 in vitro at S302, a site adjacent to its phosphotyrosine-binding (PTB) domain."
20932932
sparser
"We observed that S6K1-dependent phosphorylation of IRS1 on S307 and S1101 was diminished in SH-SY5Y cells treated with miR-200b and miR-200c."
29738527
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)."
18952604
RPS6KB1 phosphorylates IRS1 on S1101. 10 / 28
1 1 1 | 10 13 2
reach
"Western blot images showed that S6K1-dependent phosphorylation of IRS-1 on S307 and S1101, but not IRS-1 itself, were decreased in miR-200b- and miR-200c-transfected SH-SY5Y cells (Fig 5)."
29738527
sparser
"IRS1 phosphorylation at S1101 by S6K1 could play an important role in metabolic stress mechanisms and contribute to the development of IR; this phosphorylation has been cataloged as an early event in the desensitization of insulin signaling in pathological contexts [ xref , xref ]."
36224569
sparser
"S6K1 phosphorylates IRS-1 at serine 1101 [ xref , xref ] and disrupts its interaction with PI3K, leading to poor AKT activation upon insulin stimulation [ xref ]."
30296358
biopax:phosphositeplus
No evidence text available
sparser
"S6K1 kinase phosphorylates IRS1 at serine 1101 (S1101), inhibiting its function and impairing insulin signaling [ xref ]."
36224569
sparser
"We observed that S6K1-dependent phosphorylation of IRS1 on S307 and S1101 was diminished in SH-SY5Y cells treated with miR-200b and miR-200c."
29738527
reach
"S6K1 phosphorylates IRS-1 at Ser 1101 and suppresses PI3K activation."
25379019
sparser
"mTOR phosphorylates and activates S6K1, which then phosphorylates IRS-1 S1101 , leading to poor activation of its downstream PI-3 kinase as evidenced by weak binding of the PI-3 kinase to IRS-1 and weak AKT phosphorylation upon insulin stimulation [ xref , xref ]."
32998286
sparser
"Western blot images showed that S6K1-dependent phosphorylation of IRS-1 on S307 and S1101, but not IRS-1 itself, were decreased in miR-200b- and miR-200c-transfected SH-SY5Y cells ( xref )."
29738527
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."
15306821
RPS6KB1 phosphorylates IRS1 on S636. 10 / 15
1 1 2 | 10 1
reach
"IRS-1 S302 and S632 (S307 and S636, respectively, in humans) are directly phosphorylated by S6K1 and mTORC1, respectively (Copps and White, 2012)."
25813876
reach
"In addition, when mTORC1 is activated, S6K1 could directly phosphorylate Insulin receptor substrate 1 (IRS1; S307 and S636 and S639) and promote its degradation, which subsequently blunts phosphoinositide 3-kinase (PI3K)-AKT activation and its downstream effects such as glucose uptake and glycogen accumulation."
33574765
reach
"Together, this may suggest that T-cad upregulation in SHR might be a characteristic feature of hypertensive and insulin resistant VSMC phenotype.Attenuation of insulin signaling is achieved through a [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24815187
biopax:phosphositeplus
No evidence text available
reach
"P70S6K phosphorylates IRS-1 on S312 and/or S636 and S639."
23006971
reach
"Moreover, mTORC1 and S6K1 activation directly mediated the hyperphosphorylation of IRS-1 Ser636 upon alpha-Syn overexpression, while PP2A activation reversed this process in SK-N-SH cells and transgen[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25813876
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"
18498745
reach
"These results indicate that alpha-Syn overexpression negatively regulates IRS-1 at least in part by stimulating IRS-1 Ser636 phosphorylation and tyrosine dephosphorylation by mTORC1 and S6K1."
25813876
reach
"When mTORC1 is activated, S6K1 could directly phosphorylate IRS1 (S307 and S636/S639) and promote its degradation, which subsequently blunts PI3K-AKT activation and its downstream effects such as glucose uptake, glycogen accumulation, etc. [2,3]."
30011848
reach
"Inhibition of mTOR and S6K1 by HM-chromanone significantly reduced IRS-1 Ser307 and IRS-1 Ser632 phosphorylation, leading to insulin resistance."
36337245
RPS6KB1 phosphorylates IRS1 on S312. 8 / 8
| 5 3
reach
"P70S6K phosphorylates IRS-1 on S312 and/or S636 and S639."
23006971
sparser
"P70S6K can phosphorylate IRS-1 on S312 and/or S636/S639."
24931005
sparser
"P70S6K phosphorylates IRS-1 on S312 and/or S636/S639."
23006971
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."
19121779
reach
"P70S6K can phosphorylate IRS-1 on S312 and/or S636 and S639."
24931005
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)."
16953237
reach
"When alternative IRS-1 sites, S307 and S312 are phosphorylated by S6K1, it enhances proteasomal degradation, also leading to insulin resistance."
27889207
sparser
"IRS-1 is phosphorylated by S6K1 at Ser312 resulting in its dissociation from the IGF-1 receptor, and proteasome-mediated degradation ( xref )."
16953237
RPS6KB1 phosphorylates IRS1 on S639. 8 / 8
2 | 6
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."
18949383
reach
"In addition, when mTORC1 is activated, S6K1 could directly phosphorylate Insulin receptor substrate 1 (IRS1; S307 and S636 and S639) and promote its degradation, which subsequently blunts phosphoinositide 3-kinase (PI3K)-AKT activation and its downstream effects such as glucose uptake and glycogen accumulation."
33574765
reach
"Together, this may suggest that T-cad upregulation in SHR might be a characteristic feature of hypertensive and insulin resistant VSMC phenotype.Attenuation of insulin signaling is achieved through a [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24815187
reach
"P70S6K phosphorylates IRS-1 on S312 and/or S636 and S639."
23006971
reach
"When mTORC1 is activated, S6K1 could directly phosphorylate IRS1 (S307 and S636/S639) and promote its degradation, which subsequently blunts PI3K-AKT activation and its downstream effects such as glucose uptake, glycogen accumulation, etc. [2,3]."
30011848
reach
"P70S6K can phosphorylate IRS-1 on S312 and/or S636 and S639."
24931005
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."
15306821
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"
18498745
RPS6KB1 phosphorylated on S434, S441, T444, T412, S447, T252, and S394 phosphorylates IRS1 phosphorylated on S270 on S307. 5 / 5
5 |
biopax:pid
No evidence text available
17709744
biopax:pid
No evidence text available
15306821
biopax:pid
No evidence text available
11287630
biopax:pid
No evidence text available
15249583
biopax:pid
No evidence text available
18952604
RPS6KB1 phosphorylated on S434, S441, T444, T412, S447, T252, and S394 phosphorylates IRS1 phosphorylated on S270 on S1101. 5 / 5
5 |
biopax:pid
No evidence text available
15306821
biopax:pid
No evidence text available
15249583
biopax:pid
No evidence text available
17709744
biopax:pid
No evidence text available
18952604
biopax:pid
No evidence text available
11287630
RPS6KB1 phosphorylated on S434, S441, T444, T412, S447, T252, and S394 phosphorylates IRS1 phosphorylated on S270 on S636. 5 / 5
5 |
biopax:pid
No evidence text available
15306821
biopax:pid
No evidence text available
17709744
biopax:pid
No evidence text available
11287630
biopax:pid
No evidence text available
15249583
biopax:pid
No evidence text available
18952604
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."
18790744
reach
"Importantly, p70 S6K phosphorylates and inhibits IRS-1, resulting in a negative feed back to Akt and mTOR signaling."
18790744
reach
"ERK, not MTOR and p70 S6K, mediates the phosphorylation of IRS1 in the liver extracts."
19801385
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."
26993044
RPS6KB1 phosphorylates IRS1 on S270. 3 / 3
1 1 1 |
biopax:netpath
No evidence text available
18952604
biopax:phosphositeplus
No evidence text available
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."
9312143
RPS6KB1 phosphorylates IRS1 on S527. 3 / 3
1 2 |
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."
16914728
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"
18498745
biopax:phosphositeplus
No evidence text available
RPS6KB1-S6K phosphorylates IRS1 on serine. 3 / 3
| 3
reach
"For this reason, we included the same β-actin representative blot in the figures for mTOR and p70 S6K.Similarly, p70 S6K, the downstream effector of mTOR, is implicated in the serine phosphorylation of IRS-1, leading to impaired insulin signaling and insulin resistance [41]."
32664532
reach
"Additionally, p70 S6K, the downstream effector of mTOR, has been shown to cause serine phosphorylation of IRS-1, resulting in impaired insulin signaling and insulin resistance [XREF_BIBR]."
32230718
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."
26029165
RPS6KB1 phosphorylates IRS1 on tyrosine. 2 / 2
| 2
reach
"Thus, both AKT and MAPK inhibition may be potent to enhance melanoma chemosensitivity.Previous studies demonstrated that rapamycin inhibiting mTOR and thus p70S6K prevents the serine phosphorylation o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
19078992
reach
"These results indicate that alpha-Syn overexpression negatively regulates IRS-1 at least in part by stimulating IRS-1 Ser636 phosphorylation and tyrosine dephosphorylation by mTORC1 and S6K1."
25813876
Active RPS6KB1 leads to the phosphorylation of IRS1 on S1101. 2 / 2
2 |
bel
"Enhanced activation of S6K1 in CHO-Tau35 cells promoted Ser636/ Ser639 phosphorylation of IRS1, compared to both CHO and CHO-FL cells (Fig. 5c, d). S6K1 also increased IRS1 Ser1101 phosphorylation in CHO-Tau35 cells compared to CHO-FL cells (Fig. 5c, d)."
30606258
bel
"Amongst the inhibitory target phosphorylation sites on human IRS1, Ser636/Ser639 and Ser1101 (equivalent to rodent Ser632/Ser635 and Ser1097) are phosphorylated following mTORC1/S6K1 activation [50, 51]."
30606258
Active RPS6KB1 leads to the phosphorylation of IRS1. 1 / 1
1 |
bel
"mTORC1/S6K1 signaling negatively regulates insulin signaling through inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) [35]."
30606258
RPS6KB1 phosphorylated on S434, S441, T444, T412, S447, T252, and S394 phosphorylates IRS1 on S270. 1 / 1
1 |
biopax:pid
No evidence text available
18952604
Active RPS6KB1 leads to the phosphorylation of IRS1 on S639. 1 / 1
1 |
bel
"Amongst the inhibitory target phosphorylation sites on human IRS1, Ser636/Ser639 and Ser1101 (equivalent to rodent Ser632/Ser635 and Ser1097) are phosphorylated following mTORC1/S6K1 activation [50, 51]."
30606258
Active RPS6KB1 leads to the phosphorylation of IRS1 on S636. 1 / 1
1 |
bel
"Amongst the inhibitory target phosphorylation sites on human IRS1, Ser636/Ser639 and Ser1101 (equivalent to rodent Ser632/Ser635 and Ser1097) are phosphorylated following mTORC1/S6K1 activation [50, 51]."
30606258
Phosphorylated RPS6KB1 phosphorylates IRS1. 1 / 1
| 1
reach
"In our study, we found that mTORC2 deficiency could lead to increased mTORC1 activity under certain conditions [10,85] (data not shown), while over-activation of mTORC1 also restricts mTORC2 activity, either through the mTORC1-mediated phosphorylation and activation of Grb10, a negative regulator of insulin/IGF-1 receptor [12,151], or by S6K1 phosphorylation and degradation of insulin receptor substrate 1 (IRS1) to suppress mTORC2 activity [152]."
34691993
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)."
16404421