IndraLab

Statements

RPS6KB1 phosphorylates IRS1 on serine. 48 / 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
reach
"Ability of S6K1 to promote serine phosphorylation of IRS-1 has been suggested as a potential mechanism of insulin resistance [XREF_BIBR - XREF_BIBR, XREF_BIBR, XREF_BIBR]."
19781106
reach
"For example, activated S6K1 phosphorylates IRS1 on multiple serine residues."
25483727
reach
"P70 S6 kinase directly binds to and phosphorylates IRS-1 via two different serine residues, S1101 and S270."
21980324
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."
24910559
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."
27909723
reach
"Persistent activation of mTORC1 and S6K1 induce serine phosphorylation of insulin receptor substrate 1 (IRS-1) and IRS-2."
30333180
reach
"Adiponectin sensitizes insulin signaling by reducing p70 S6 kinase mediated serine phosphorylation of IRS-1."
17244624
rlimsp
"This pathway is under both positive and negative regulation, including S6 kinase (S6K) phosphorylation of insulin receptor substrate-1 (IRS-1) at S636/639, which occurs downstream of mammalian target of rapamycin (mTOR) activation to inhibit this adapter protein."
20179297
reach
"Reduced mTOR and S6K1 signaling during chronic increases in physical activity may play an important regulatory role in the serine phosphorylation of IRS-1, which should be examined as a potential mechanism for attenuation of insulin resistance associated with increased IRS-1 serine phosphorylation."
18347658
reach
"In addition to stimulating muscle anabolism, activated mTORC1 and S6K1 can phosphorylate insulin receptor substrate 1 (IRS-1) on serine residues, which can lead to insulin resistance."
24997070
sparser
"Recent studies demonstrate that the mTOR downstream target S6K1 directly phosphorylates IRS1 serine residues, including Ser-302/307 ( xref ), Ser-307/312 ( xref ), Ser-632/636 ( xref ), and Ser-1097/1101 ( xref )."
21282364
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
rlimsp
"Once activated by insulin, mTOR/p70S6K phosphorylates insulin receptor substrate-1 (IRS-1) on serine residues, resulting in its inhibition and reduction of insulin signaling."
21602475
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."
28691706
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)."
25706655
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
"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."
21294052
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."
25483727
reach
"Conversely, silencing of S6K1 using siRNAs was shown to decrease IRS-1 phosphorylation on several serine residues leading to an increase in PI3K and AKT signaling."
23898460
reach
"This was due to increased basal S6K1 activity which leads to IRS1 serine phosphorylation and disruption of PI 3-kinase activation, thereby limiting the effects of insulin on fatty acid uptake and lipolysis."
22221695
sparser
"mTORC1 and its substrate S6K1 participate in a well-documented feedback loop xref in which growth factor and nutrient signaling limits the activity of the PI3K/Akt pathway: S6K1 phosphorylates IRS-1 on serine residues that promote its ubiquitination and degradation."
21454807
reach
"For example, IL-6-dependent insulin resistance is mediated, at least in part, by induction of SOCS3 in insulin target cells, which inhibits tyrosine phosphorylation of IRS; TNFalpha is a potent activator of JNK, which in turn phosphorylates IRS-1 at Ser 307; adiponectin sensitizes insulin signaling by reducing p70 S6 kinase mediated serine phosphorylation of IRS-1."
20395945
reach
"In vitro studies with rapamycin suggest that mTOR and S6K1 overactivation contributes to elevated serine phosphorylation of IRS-1, leading to impaired insulin signaling to Akt in liver and muscle of this dietary model of obesity."
15604215
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
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]."
22391948
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]."
21680199
reach
"XREF_BIBR In obese rodents, hyperactive mTORC1 and S6K1 induces IRS-1 phosphorylation at serine residues and consequent IRS-1 degradation, leading to the impairment of PI3K-Akt signaling."
32821100
sparser
"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 – xref ."
29330362
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
"This impairment correlated with increased phosphorylation of mTOR, p70S6K and serine phosphorylation of IRS-1 [XREF_BIBR]."
32230718
reach
"In a complementary pathway, S6K1 phosphorylates IRS-1 on serine residues leading to its degradation and also phosphorylates rictor, a protein unique to mTORC2."
24018049
sparser
"This kind of feedback regulation is known to limit insulin signaling through the phosphorylation of IRS1 by p70 S6 kinase at Ser residues ( xref )."
20736484
sparser
"mTORC1 is able to impair insulin signaling via its substrates S6K1 which then phosphorylates serine residues of IRS1 causing downregulation of PI3K/Akt pathway (Harrington et al., xref ; Shah et al., xref )."
28659828
sparser
"As such, S6K1 phosphorylates IRS-1 proteins at several serine residues (S270, S307, S636, and S1101) of which S270 was found to be required for S6K1/IRS-1 interaction and subsequent phosphorylation of the other S6K1-specific residues [ xref ]."
32932888
reach
"P70S6K can also phosphorylate IRS1 on an inhibitory serine residue, thus causing negative feedback that inhibits insulin and IGF signaling to PI3K and AKT."
27758884
sparser
"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
reach
"mTORC1 and its substrate S6K1 participate in a well documented feedback loop 35 in which growth factor and nutrient signaling limits the activity of the PI3K and Akt pathway : S6K1 phosphorylates IRS-1 on serine residues that promote its ubiquitination and degradation."
21454807
reach
"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