IndraLab

Statements

RPS6KB1 phosphorylates IRS1. 152 / 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
reach
"An experiment using dominant negative S6K1 supports the essential role of S6K1 in the hyperosmolarity stimulated phosphorylation of IRS1."
18252807
reach
"mTOR phosphorylates and activates S6K1, which in turn phosphorylates IRS-1 causing its internalization (Um et al., 2004)."
29729422
reach
"Nonetheless, upon growth factor stimulation, mTORC1 activates S6K1, which in turn phosphorylates IRS-1 at the plasma membrane, and ultimately suppresses PI3K mediated activation of AKT."
21179025
sparser
"Phosphorylation of IRS-1 by S6K1 inhibits its interaction with insulin and IGF receptors and also promotes proteasomal degredation of IRS-1 ( xref ), thereby dampening PI3K signalling and reducing AKT activity."
27919797
reach
"mTORC1 activation is postulated to cause a negative feedback loop through S6K1, which directly phosphorylates IRS-1 and finally induces its degradation XREF_BIBR."
22059905
reach
"However an alternate event, p70 S6 kinase phosphorylation of IRS-1 on S636/639, could also occur resulting in decreased IGF-1R signaling."
21980324
reach
"S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T, P sites."
16914728
sparser
"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 xref ."
29416044
sparser
"The insulin receptor substrate 1 (IRS1) is directly phosphorylated by S6K1 at multiple sites which impairs its function and leads to inhibitory effects on the insulin-PI3K-AKT pathway."
25505994
sparser
"Rapamycin inhibits S6K1-dependent IRS-1 serine phosphorylation, increases IRS-1 protein levels, and promotes association of tyrosine-phosphorylated IRS-1 with PI3K. A rapamycin-resistant S6K1 mutant prevents rapamycin-induced Akt activation and VSMC differentiation."
17908691
sparser
"Although it has been proposed that adiponectin may insulin sensitize through reduced serine phosphorylation of IRS1 by p70S6 kinase ( xref ), our in vivo data are not consistent with this model."
22989629
reach
"Notably, activated p70S6K can phosphorylate insulin receptor substrate IRS-1, an activator of PI3K, and induce IRS-1 degradation, followed by the suppression of PI3K activity."
26314828
reach
"When mTORC1 is active, p70S6K phosphorylates the IRS-1 and -2 proteins on Ser residues, targeting them for proteasomal degradation [XREF_BIBR, XREF_BIBR]."
22564882
sparser
"There were also positive correlations between interventions in the insulin signalling pathway, particularly betweenIrs1 −/− andRps6kb1 −/− mutants, which is interesting considering that Rps6kb1 directly phosphorylates and inhibits Irs1 ( xref )."
33454277
sparser
"For example, the negative feedback loop in which S6K1 promotes the phosphorylation of IRS1 and this way reduces its stability [ xref ]."
25152703
reach
"Insulin activates mTORC1 and its substrate S6K1, which phosphorylates and inhibits the insulin receptor substrate 1 (IRS-1)."
25161886
sparser
"In cell lines, it has been shown that IRS1 stability can be regulated by a negative feedback loop wherein S6K1 phosphorylates IRS1, targeting it for degradation by the proteasome ( xref )."
18755774
sparser
"Notably, activated p70S6K can phosphorylate insulin receptor substrate IRS-1, an activator of PI3K, and induce IRS-1 degradation, followed by the suppression of PI3K activity."
26314828
sparser
"S6K1 phosphorylates IRS-1 causing disruption in IR signal transduction."
31363792
reach
"Activation of mTORC1 can inhibit the PI3K and AKT pathway through a negative feedback loop mediated by p70S6K phosphorylation of insulin receptor substrate 1."
26233890
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]."
25026290
sparser
"In a complementary pathway, S6K1 phosphorylates IRS-1 on serine residues leading to its degradation ( xref ) and also phosphorylates rictor, a protein unique to mTORC2 ( xref )."
24018049
sparser
"S6K1 phosphorylates inhibitory serine sites of IRS-1 leading to its degradation ( xref – xref ), whereas rapamycin prevents inhibitory IRS-1 phosphorylation, stabilizing IRS-1 and induces Akt activity by augmenting IGF-IR signaling to PI3K/Akt."
21294052
reach
"Since both mTOR and S6K1 can phosphorylate IRS1 we wanted to determine the affects of Shh on the activation of S6K."
18755774
reach
"Increased BCAAs may increase activation of mTOR and S6K1 kinase pathway, which phosphorylates insulin receptor substrate 1 (IRS-1), with a subsequent decline in IRS-1 associated phosphatidylinositide 3-kinase (PI 3-kinase) activity."
25781947
sparser
"Adiponectin enhances insulin signaling by reducing p70 S6 kinase-mediated serine phosphorylation of IRS-1 [ xref ] but systemic adiponectin levels are not influenced by carbohydrate uptake."
17311679
trips
"Notably, rictor and IRS-1 phosphorylation by p70S6K1 attenuate insulin action through a negative feedback pathway."
27965359
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
"There were also positive correlations between interventions in the insulin signalling pathway, particularly between Irs1 -/- and Rps6kb1 -/- mutants, which is interesting considering that Rps6kb1 directly phosphorylates and inhibits Irs1."
33454277
sparser
"Nonetheless, upon growth factor stimulation, mTORC1 activates S6K1, which in turn phosphorylates IRS-1 at the plasma membrane, and ultimately suppresses PI3K-mediated activation of AKT ( xref ; xref )."
21179025
reach
"However, we also need to consider that this would generate sustained p70S6K activation, which should phosphorylate IRS1, causing insulin desensitization and interrupted Akt activation, an apparent contradiction to what was reported in post-mortem AD brain."
28626421
reach
"Loss-of-function and pharmacological inhibition studies have shown that the mTOR target S6K1, for instance, inhibits and desensitizes insulin-PI3K signaling by phosphorylating IRS1 protein and suppressing IRS1 gene transcription."
21962509
reach
"Here, we show that MASTL/Greatwall, a cell cycle kinase that supports mitosis by phosphorylating the PP2A/B55 inhibitors ENSA/ARPP19, inhibits PI3K-AKT activity by sustaining mTORC1- and S6K1-dependent phosphorylation of IRS1 and GRB10."
36354735
reach
"Notably, rictor and IRS-1 phosphorylation by p70S6K1 attenuate insulin action through a negative feedback pathway."
27965359
sparser
"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 ( xref )."
26993044
reach
"mTOR inhibition prevents negative feedback mechanisms; in one of these S6K1 phosphorylates IRS-1 (insulin receptor substrate-1) causing it to dissociate from tyrosine kinase receptors; in another mTORC1 phosphorylates GRB10 which suppresses insulin and IGF receptor kinase activity and facilitates their degradation; and in a third mTORC2 assembly is prevented by phosphorylation of Sin1, mediated by S6K or Akt depending on the cell type."
26793165
sparser
"The use of specific inhibitors to block AT 1 R-induced EGFR transactivation confirmed that Ang II/AT 1 R-induced S6K-1 Thr 421 /Ser 424 and IRS-1 Ser 636 /Ser 639 phosphorylation are dependent on activation of PKC, MMPs and EGFR transactivation ( xref )."
19879250
trips
"S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites."
16914728
sparser
"It is well known that chronic treatment with growth factors induces a negative feedback regulation on IRS1 via the mTOR/S6K1 pathway, leading to S6K1-dependent phosphorylation of IRS1."
23304509
sparser
"It has been shown that p70S6K downstream of TORC1 can phosphorylate and inhibit the insulin receptor substrate IRS1 (Harrington et al. xref ) and that sustained activation of TORC1 leads to depletion of IRS1 and IRS2 and insulin resistance (Shah et al. xref )."
28643116
sparser
"Upon activation by growth factors, mTORC1 limits the extent of upstream growth factor signaling by a negative feedback loop through IRS-1 phosphorylation by S6K1[ xref , xref ]."
27033070
sparser
"S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites."
16914728
reach
"Akt indirectly activates p70S6K, which then phosphorylates IRS1, thereby suppressing PI3K activation."
27390173
sparser
"Thus, phosphorylation of IRS1(Ser307, 1101) by hyperactive S6K1, and phosphorylation of IRS1(Ser636/639, 422) by hyperactive mTORC1, result in suppressing IRS tyrosines phosphorylation by the IR tyrosine kinase, followed by IRS ubiquitination and degradation [ xref – xref ]."
32128655
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
sparser
"In our study, we found that mTORC2 deficiency could lead to increased mTORC1 activity under certain conditions [ xref , xref ] (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 [ xref , xref ], or by S6K1 phosphorylation and degradation of insulin receptor substrate 1 (IRS1) to suppress mTORC2 activity [ xref ]."
34691993
reach
"Negative regulation of mTORC1 by AMPK can increase insulin sensitivity by repressing p70S6K1 phosphorylation and inactivation of IRS1."
21723507
sparser
"In contrast, sustained PI3K/Akt activation inhibits IRS1 activity by negative feedback through the activation of mTOR and p70S6K that phosphorylate IRS1 on its inhibitory domain (Ser 307 ) [ xref ]."
24735980
sparser
"S6K1 also phosphorylates and inactivates IRS1, thereby providing a negative feedback loop [ xref ]."
24352740
reach
"S6K1 also phosphorylates and inactivates IRS1, thereby providing a negative feedback loop [XREF_BIBR]."
24352740
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."
23459195
reach
"21 S6K1 also phosphorylates insulin receptor substrate 1 (IRS1) 22 and mTOR 23 in response to nutrients and growth factors, albeit in a feedback fashion."
25229342
sparser
"We report here that Ang II-induced IRS-1 Ser 636 /Ser 639 phosphorylation by S6K-1 is involved in the inhibition of Akt."
19879250
sparser
"However an alternate event, p70 S6 kinase phosphorylation of IRS-1 on S636/639, could also occur resulting in decreased IGF-1R signaling."
21980324
sparser
"As a negative-feedback loop exists in which S6K1 directly phosphorylates IRS1 (insulin receptor substrate protein 1) and blocks IGF-1 (insulin-like growth factor 1) signaling to PI3K xref , a major drawback of selectively inhibiting mTOR is the consequent activation of PI3K, which can ultimately enhance tumor growth xref ."
21110697
sparser
"These apparent paradoxical events are linked to a negative feedback loop in which hyperactive S6K1 phosphorylates the insulin receptor substrate-1 (IRS-1), thereby leading to the internalization of th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29729422
reach
"Insulin- and amino acid-mediated activation of mTOR/S6K via the PI3K pathway leads to a negative feedback loop resulting in the phosphorylation and downregulation of IRS1 by S6K1 and eventually insulin resistance and type 2 diabetes."
32054043
reach
"Following activation, mTORC1 phosphorylates and activates its downstream target p70S6K, which then phosphorylates and inhibits IRS1, the upstream of PI 3-K [XREF_BIBR]."
21307646
sparser
"These apparent paradoxical events are linked to a negative feedback loop in which hyperactive S6K1 phosphorylates the insulin receptor substrate-1 (IRS-1), thereby leading to the internalization of the receptor and insulin resistance ( xref )."
29729422
reach
"It has been described that S6K1 phosphorylates insulin receptor substrate 1 (IRS-1), promoting its degradation."
20628002
sparser
"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. [ xref , xref ]."
30011848
sparser
"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 , xref ]."
22391948
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 "
26432419
sparser
"Akt mediated activation of mTOR results in activation of p70S6K, which phosphorylates IRS-1 resulting in inhibition of IRS1."
19690459
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)."
15249583
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."
23396401
reach
"S6K1 phosphorylates IRS-1 causing disruption in IR signal transduction."
31363792
sparser
"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."
17709744
sparser
"Upon activation, mTORC1 activates S6K1, which in turn phosphorylates inhibitory sites (i.e. Ser 636/639) on the insulin receptor substrate-1 (IRS-1), thereby suppressing IRS-1 mediated activation of t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
20005306
sparser
"Lastly, IR in AD brain is linked to inhibitory feedback phosphorylations of IRS-1 (S616 and S636) by pS6K [ xref , xref ]."
35061720
sparser
"As part of a negative feedback loop, S6K1 also phosphorylates and inhibits insulin receptor substrate 1 (IRS-1), leading to inhibition of AKT (protein kinase B)-mTOR and extracellular signal-regulated kinase (ERK) signaling."
23607966
reach
"Moreover, genetic deletion of S6K1 in mice fed with a high fat diet prevented both insulin resistance and serine 1101 phosphorylation of IRS1 10."
33303821
reach
"The best described negative feedback mechanism occurs through S6K1, which directly phosphorylates insulin receptor substrate 1 causing its mislocalization and degradation (XREF_FIG)."
20418915
sparser
"Given that p70S6K phosphorylates IRS-1 and induces its degradation ( xref , xref ), we postulate that the inactivation of p70S6K by miR-200 in lung cancer cells may feedback activate AKT by increasing IRS-1 ( xref )."
26314828
sparser
"Insulin- and amino acid-mediated activation of mTOR/S6K via the PI3K pathway leads to a negative feedback loop resulting in the phosphorylation and downregulation of IRS1 by S6K1 and eventually insulin resistance and type 2 diabetes."
32054043
sparser
"In addition, when mTORC1 is activated, S6K1 could directly phosphorylate Insulin receptor substrate 1 (IRS1; S307 and S636/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 ( xref ; xref )."
33574765
reach
"49 Active mTORC1 and S6K1 phosphorylate insulin receptor substrate 1 (IRS1), which is an adaptor protein that recruits key downstream effectors to the insulin receptor."
27534530
reach
"To control the extent of mTORC1 activation and restore TSC regulation after this stimulus, the mTORC1 substrate S6K1 then directly phosphorylates insulin receptor substrate 1 (IRS-1) as part of a negative feedback loop, blocking the further insulin mediated activation of the PI3K-AKT pathway [XREF_BIBR, XREF_BIBR]."
33572326
reach
"For example, the negative feedback loop in which S6K1 promotes the phosphorylation of IRS1 and this way reduces its stability [XREF_BIBR]."
25152703
reach
"Rapamycin treatment also resulted in an increased mobility of IRS1, indicating that S6K1 contributes to the basal phosphorylation of IRS1."
23304509
sparser
"Studies in cultured myotubes and isolated rat skeletal muscles suggest that Leu and BCAA can impair insulin-mediated glucose uptake through a negative-feedback loop (Iwanaka et al. 2010; xref ), presumably mediated by mTOR-S6K1 phosphorylation and subsequent serine phosphorylation and inactivation of IRS-1 (Iwanaka et al. 2010; xref )."
29728917
reach
"As shown in XREF_FIG, 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."
23396401
reach
"S6K1 and mTORC1 phosphorylate IRS-1 directly to induce its degradation, thus uncoupling the insulin receptor from PI3K."
25242279
sparser
"When activated by mTORC1, S6K1 directly phosphorylates the insulin receptor substrate-1 (IRS1), which promotes IRS1 degradation and reduces the ability of growth factors to signal downstream of receptor tyrosine kinase (RTK) ( xref ; xref ) ( xref )."
22500797
reach
"The observation of increased AKT phosphorylation upon dexamethasone treatment may indicate there is activation of the known negative feedback loop consisting of S6K1 phosphorylation and downregulation of IRS1."
26080839
reach
"In addition, mTOR and S6K1 have been shown to induce serine/threonine phosphorylation of IRS1 to attenuate signal flow to downstream effectors, and thus play a role in insulin resistance [XREF_BIBR]."
20167101
reach
"Increased activation of mTOR results in activation of p70S6K, which phosphorylates IRS1 resulting in inhibition of IRS1."
19435890
reach
"The results show that only in IRS-1 108-516 in which serines 302, 307, and 310 are mutated (XREF_FIG A, site 2) is IRS-1 not phosphorylated in vitro by S6K1 (XREF_FIG C, left panels)."
15249583
sparser
"Here, we show that MASTL/Greatwall, a cell cycle kinase that supports mitosis by phosphorylating the PP2A/B55 inhibitors ENSA/ARPP19, inhibits PI3K-AKT activity by sustaining mTORC1- and S6K1-dependent phosphorylation of IRS1 and GRB10."
36354735
reach
"The insulin receptor substrate 1 (IRS1) is directly phosphorylated by S6K1 at multiple sites which impairs its function and leads to inhibitory effects on the insulin-PI3K-AKT pathway."
25505994
reach
"For example, S6K1 can phosphorylate IRS-1 to inhibit insulin receptor signaling [XREF_BIBR]."
21805467
sparser
"The observation of increased AKT phosphorylation upon dexamethasone treatment may indicate there is activation of the known negative feedback loop consisting of S6K1 phosphorylation and downregulation of IRS1 ( xref )."
26080839
reach
"These apparent paradoxical events are linked to a negative feedback loop in which hyperactive S6K1 phosphorylates the insulin receptor substrate-1 (IRS-1), thereby leading to the internalization of th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29729422
sparser
"In humans, acute supplementation with protein has been shown to be insulinotropic. xref , xref , xref It has been suggested that the insulinotropic effect of leucine is mediated by stimulation of protein synthesis in pancreatic β cells by the mTOR signaling pathway. xref This pathway mediates insulin resistance by phosphorylation of IRS-1 by S6K1."
28969366
reach
"In fact, S6K1 (activated by mTORC1) promotes also the phosphorylation and inactivation of IRS1, the insulin receptor substrate 1."
25685786
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."
29416044
reach
"In cell lines, it has been shown that IRS1 stability can be regulated by a negative feedback loop wherein S6K1 phosphorylates IRS1, targeting it for degradation by the proteasome."
18755774
sparser
"Next, the resistance to insulin/IGF action that characterizes AD brain has been mechanistically linked to the inhibitory feedback phosphorylations of IRS-1 (S616 and S636) by pS6K [ xref , xref ]."
34215308
rlimsp
"S6K1 phosphorylates IRS1 in vitro on multiple residues showing strong preference for RXRXXS/T over S/T,P sites."
16914728
sparser
"S6K1 can phosphorylate and inactivate IRS1, thereby allowing a feedback regulation of the IRS1/PI3K/AKT pathway [ xref , xref , xref ]."
26999118
reach
"Specifically, the mTORC1 substrate, S6K1, phosphorylates IRS-1 at S636/639 to promote its degradation, which in turn, reduces PI3K and Akt signaling."
31710966
sparser
"Persistent inhibition of S6K1 has been shown to activate Akt via feedback inhibition of the PI3K pathway where S6K1 phosphorylates several sites on insulin receptor substrate-1 (IRS-1) and inhibits it ( xref – xref )."
21427355
reach
"S6K1 can phosphorylate and inactivate IRS1, thereby allowing a feedback regulation of the IRS1/PI3K/AKT pathway [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
26999118
reach
"As a negative-feedback loop exists in which S6K1 directly phosphorylates IRS1 (insulin receptor substrate protein 1) and blocks IGF-1 (insulin like growth factor 1) signaling to PI3K 107, a major drawback of selectively inhibiting mTOR is the consequent activation of PI3K, which can ultimately enhance tumor growth 108."
21110697
reach
"In vitro studies demonstrated that S6K1 phosphorylates mouse (m) S302 and mS522 (human (h) S307 and hS527) of IRS-1 [XREF_BIBR], and mTORC1 phosphorylates mS632 (hS636) of IRS-1 [XREF_BIBR]."
29077002
reach
"When activated by mTORC1, S6K1 directly phosphorylates the insulin receptor substrate-1 (IRS1), which promotes IRS1 degradation and reduces the ability of growth factors to signal downstream of receptor tyrosine kinase (RTK) (XREF_FIG)."
22500797
sparser
"Both mTORC1 and S6K1 could phosphorylate IRS-1 ()."
30240640
reach
"The findings of the present study of diet-and obesity induced insulin resistance in murine models suggest that suppression of TSC1 by IKKbeta activates mTOR and S6K1, which in turn phosphorylate IRS1 at Ser636/639 and Ser307, thereby inhibiting IRS1 function)."
18949383
sparser
"S6K1 and mTORC1 phosphorylate IRS-1 directly to induce its degradation, thus uncoupling the insulin receptor from PI3K."
25242279
sparser
"Since both mTOR and S6K1 can phosphorylate IRS1 we wanted to determine the affects of Shh on the activation of S6K. Western blot analysis ( xref ) shows that S6K phosphorylation, an indicator of its activation by mTOR, is reduced in Shh-treated CGNPs."
18755774
sparser
"S6K1-dependent serine phosphorylation of IRS-1."
29738527
reach
"In aortic endothelial cells, ANG II can stimulate mTOR and p70S6K activation that phosphorylates IRS1 and inhibits endothelial nitric oxide synthase that not only may contribute to insulin resistance but also to vasoconstriction and hypertension [XREF_BIBR]."
22545721
reach
"In turn, S6K1 activation suppresses PI3K signaling through an intracellular negative feedback loop in which pS6K1 phosphorylates insulin receptor substrate 1 (IRS1) and targets it for degradation through ubiquitin mediated mechanisms, extinguishing its PI3K activating actions."
28099079
sparser
"The findings of the present study of diet-and obesity-induced insulin resistance in murine models suggest that suppression of TSC1 by IKKβ activates mTOR and S6K1, which in turn phosphorylate IRS1 at Ser636/639 and Ser307, thereby inhibiting IRS1 function)."
18949383
sparser
"S6K1, a major target of mTOR, is required for IRS1 phosphorylation in cells and can also directly phosphorylate IRS1 ( xref ; xref )."
18755774
reach
"Upon activation, mTORC1 activates p70S6 kinase (S6K1), a key mTORC1 substrate, which in turn phosphorylates IRS1 at multiple serine residues that disrupt IRS1 activity XREF_BIBR - XREF_BIBR."
29330362
sparser
"P70S6K phosphorylates IRS1 (insulin receptor substrate)."
21670491
reach
"On the other hand, the mTORC1 substrate RPS6KB1 phosphorylates and inhibits IRS1 [XREF_BIBR, XREF_BIBR]."
33544134
reach
"S6K1, a major target of mTOR, is required for IRS1 phosphorylation in cells and can also directly phosphorylate IRS1."
18755774
reach
"P70S6K phosphorylates IRS1 (insulin receptor substrate)."
21670491
sparser
"Prompted by the results from intravenous amino acid infusion studies in people that demonstrated that amino acids blunt insulin-mediated glucose disposal ( xref , xref ) and studies conducted in cultured myotubes and isolated rat skeletal muscles that demonstrated that leucine can impair insulin-mediated glucose uptake ( xref , xref ), presumably mediated by mTOR-p70S6K phosphorylation and subsequent serine phosphorylation of insulin receptor substrate-1 ( xref ), we tested the hypothesis that protein ingestion impairs insulin-mediated glucose disposal by leucine-mediated muscle mTOR signaling in people."
25999540
sparser
"Increased activation of mTOR results in activation of p70S6K, which phosphorylates IRS1 resulting in inhibition of IRS1."
19435890
sparser
"P70S6K is activated in the insulin-signaling pathway via AKT phosphorylation of mTOR, which in turn phosphorylates and activates p70S6K. A well defined negative signaling pathway has been described involving negative phosphorylation of IRS-1 by p70S6K, leading to insulin induced degradation of IRS-1 ( xref ; xref )."
26868295
sparser
"In fact, S6K1 (activated by mTORC1) promotes also the phosphorylation and inactivation of IRS1, the insulin receptor substrate 1."
25685786
sparser
"It has been described that S6K1 phosphorylates insulin receptor substrate 1 (IRS-1), promoting its degradation ( xref )."
20628002
sparser
"We observed that Ang II induced a transitory increase in IRS-1 Ser 636 /Ser 639 and S6K-1 Thr 421 /Ser 424 phosphorylation."
19879250
reach
"IL-6 activates S6K1 in these cells, but unexpectedly, S6K1 is not involved in IL-6 inhibition of insulin signaling, since the effect of IL-6 persists in cells with drastically reduced S6K1 levels induced by RNA interference, suggesting that the function of mTOR signaling is through a mechanism different from the prevailing model of S6K1 phosphorylation of insulin receptor substrate-1."
17993646
reach
"It is well known that chronic treatment with growth factors induces a negative feedback regulation on IRS1 via the mTOR and S6K1 pathway, leading to S6K1 dependent phosphorylation of IRS1."
23304509
reach
"It has been shown that p70S6K downstream of TORC1 can phosphorylate and inhibit the insulin receptor substrate IRS1 and that sustained activation of TORC1 leads to depletion of IRS1 and IRS2 and insulin resistance."
28643116
reach
"As metformin treatment is known to induce glucose uptake in skeletal muscle, it was hypothesized that, at least in part, these effects are mediated by metformin induced activation of the AMPK-TSC1/2 axis and inhibition of mTORC1 and S6K1 phosphorylation of IRS1."
20444419
sparser
"The best-described negative feedback mechanism occurs through S6K1, which directly phosphorylates insulin receptor substrate 1 causing its mislocalization and degradation ( xref )."
20418915
reach
"Adiponectin enhances insulin signaling by reducing p70 S6 kinase mediated serine phosphorylation of IRS-1 [XREF_BIBR] but systemic adiponectin levels are not influenced by carbohydrate uptake."
17311679
reach
"Inhibition of S6K1 activity prevents phosphorylation of IRS-1 (S636/639), resulting in accumulation of IRS-1 and activation of its downstream kinases, such as PI3K and Akt, by a feedback regulating mechanism."
20628002
sparser
"This impairment correlated with increased phosphorylation of mTOR, p70S6K and serine phosphorylation of IRS-1 [ xref ]."
32230718
sparser
"Attenuation of insulin signaling is achieved through a negative feedback loop involving Akt-dependent stimulation of mTOR complex with Raptor mTORC1 and its effector kinase S6K1 which phosphorylates I[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
24815187
sparser
"However, S6K1 has multiple substrates. xref For example, S6K1 phosphorylates eEF2K to enhance protein synthesis, xref and the cell growth regulator SKAR (S6K1 Aly/REF-like target) has also been identified as a substrate for S6K1, but not for S6K2. xref S6K1 also phosphorylates insulin receptor substrate 1 (IRS1) xref and mTOR xref in response to nutrients and growth factors, albeit in a feedback fashion."
25229342
reach
"As part of a negative feedback loop, S6K1 also phosphorylates and inhibits insulin receptor substrate 1 (IRS-1), leading to inhibition of AKT (protein kinase B)-mTOR and extracellular signal-regulated kinase (ERK) signaling."
23607966
reach
"In turn, the activation of p70S6K by mTORC1 promotes the phosphorylation of IRS1 and reduces its stability, an auto-regulatory pathway or negative feedback loop that has been shown to have profound implications for both metabolic diseases and tumorigenesis [XREF_BIBR, XREF_BIBR]."
26536660
reach
"Given that p70S6K phosphorylates IRS-1 and induces its degradation, we postulate that the inactivation of p70S6K by miR-200 in lung cancer cells may feedback activate AKT by increasing IRS-1 (XREF_FIG)."
26314828
reach
"But beside its phosphorylation at this site, IRS-1 can be down-regulated through transcriptional repression 42 and phosphorylated at different residues by S6K1 as well as by other members of the pathway XREF_BIBR - XREF_BIBR."
19098454
sparser
"Furthermore, S6K1 serine phosphorylates IRS1 and IRS2 thereby decreasing insulin signaling ( xref )."
19797661
reach
"Specifically, mTORC1 activation negatively feeds back to PI3K by S6K1 phosphorylation of IRS1 and by regulating Grb10 stability via direct phosphorylation [XREF_BIBR - XREF_BIBR]."
25646773