IndraLab

Statements


1 4 | 4 50

sparser
"As shown in xref , the 30-AA mutant peptide inhibited the interaction between p110α E545K and IRS1 when added into cell lysates, whereas the WT peptide failed to cause any inhibition."

sparser
"Our data demonstrate that the p110α helical domain mutant proteins gain interaction with IRS1 in the absence of growth factor stimulation and that this mutant-specific protein interaction is independent of binding of p85 to phospho-IRS1 (see xref for our proposed model)."

sparser
"IRS1-p110α E545K interaction brings the mutant p110α to cytoplasmic membrane."

No evidence text available

sparser
"This IRS1-p110α E545K interaction was validated by immunoprecipitation under serum-starvation conditions in three different settings."

reach
"We found that, when FBXL2 expression was silenced in NHFs, endogenous IRS1 bound more endogenous p85beta, but less p110alpha and p110beta (XREF_FIG)."

sparser
"It appeared that the p110α E545K-IRS1 interaction also did not require p85, as a truncated p110α E545K lacking the ABD domain required for p85 binding ( xref ) still associated with IRS1 ( xref and xref )."

sparser
"This action involved a PR (proline rich) domain-dependent interaction of PRR11 with the p85 regulatory subunit of PI3K which reduces homodimerization of p85 and, in turn, is permissive of ligand-induced association of p110α with insulin receptor substrate 1 (IRS1) and activation of PI3K. Ectopic expression of PRR11 failed to promote estrogen-independent growth when p110α was knocked down, and PRR11 -overexpressing cells were highly sensitive to PI3K inhibitors, suggesting that PRR11 amplification generates dependence on PI3K signaling, particularly in the setting of estrogen deprivation."

sparser
"Interestingly, as shown in xref , the stapled mutant peptide also inhibited the interaction between IRS1 and ΔABD p110α E545K. Thus this result provided further evidence that the protein interaction between IRS1 and p110α E545K mutant is not mediated by p85."

No evidence text available
IRS1 binds mutated PIK3CA. 3 / 3
| 3

reach
"Interaction between the helical domain mutant p110alpha and IRS1 does not require p85 or IRS1 phosphorylation."

reach
"In support of earlier results, it was also notable that the stapled mutant peptide did slightly reduce the protein levels of p110alpha, but did not affect levels of p85 and IRS1 (XREF_FIG and XREF_SUPPLEMENTARY), providing further evidence that the protein interaction between mutant p110alpha and IRS1 stabilizes p110alpha."

reach
"We then tested if peptides corresponding to only one of the two alpha-helical motifs could inhibit interactions between the mutant p110alpha and IRS1."

sparser
"We show here that the p110α helical domain mutants, but not the kinase domain mutant, directly associate with IRS1 without growth factor stimulation."

sparser
"P110α helical domain mutants, but not the kinase domain mutants, interact with IRS1."
| 2

sparser
"These findings suggest that IGF-I-induced association of p110α with IGF-IR and IRS-1 is enhanced when p110β levels are reduced."

sparser
"Our results suggest that p110β deficiency leads to increased Akt activation through two separate mechanisms: First, reduced p110β levels enhance the IGF-I-induced association of p110α with IGF-IR and IRS-1."
| 2

sparser
"In p110α-deficient cells, IGF-I-induced association of both p110α and p110β with IGF-IR and IRS-1 was reduced, whereas in p110β-deficient cells, association of p110α with IGF-IR and IRS-1 was enhanced ( xref , right)."

sparser
"Simultaneous knockdown of p110α and p110β prevented IGF-I induced association of both p110α and p110β with IGF-IR and IRS-1."
IRS1 binds PIK3CA-E545K. 2 / 2
| 2

reach
"To this end, we discovered that IRS1 binds to p110alpha E545K mutant but not to WT or H1047R mutant under serum starvation conditions."

reach
"Moreover, when IRS1 was immunoprecipitated from various DLD1 derivatives, p110alpha E545K predominantly associated with IRS1 (XREF_FIG and XREF_SUPPLEMENTARY)."
| 2

sparser
"Moreover, we observed that valsartan treatment exaggerated the insulin-induced phosphorylation of IRS-1, the association of IRS-1 with the p85 regulatory subunit of phosphoinositide 3 kinase (PI 3-K), PI 3-K activity, and translocation of GLUT4 to the plasma membrane."

sparser
"As expected, compared with normal chow-fed mice, insulin-induced AKT phosphorylation, tyrosine phosphorylation of IRS1 (insulin receptor substrate 1), and IRS1 interaction with p85-phosphoinositide 3 kinase (PI3K) were greatly reduced in adipose tissue, liver, and muscle of HFD-fed wild-type control mice ( xref ), demonstrating diet-induced insulin insensitivity of these tissues."
| 1

sparser
"In contrast, insulin-stimulated binding of the p85 (regulatory) and p110α (catalytic) subunits of PI3K to Irs1 was significantly reduced in A/lox::LKO2 hepatocytes (p<0.05)."
IRS1 binds PIK3CA and CRC. 1 / 1
| 1

sparser
"Moreover, the p110α E545K stapled peptide also disrupted protein interaction between p110α Q546P and IRS1 in Vaco481 CRC cells ( xref and xref ), suggesting that these helical domain mutant proteins share a common critical protein interaction interface with IRS1."
| 1

sparser
"In p110α-deficient cells, IGF-I-induced association of both p110α and p110β with IGF-IR and IRS-1 was reduced, whereas in p110β-deficient cells, association of p110α with IGF-IR and IRS-1 was enhanced ( xref , right)."
IRS1 binds PIK3CA and DLD1. 1 / 1
| 1

sparser
"Importantly, when added to cell culture medium, the stapled mutant peptide effectively disrupted IRS1-p110α E545K interaction in DLD1 cells at 50 μM concentration ( xref and xref ), demonstrating both targeting activity and cell permeability of this stapled peptide."
| 1

sparser
"Biochemical analyses have shown that both PIK3CA E545K and PIK3CA H1047R exhibit ~two-fold higher catalytic activity than wild type PI3K. The association of PIK3CA H1047R with PDGFR or IRS-1 phosphopeptides further increases the catalytic activity of the mutant enzyme ( xref )."
AKT binds INS, IRS1, and PIK3CA. 1 / 1
| 1

sparser
"This was associated with increased glucose transporter-4 translocation into the plasma membrane via enhancing insulin signaling pathways and the insulin receptor substrate-1-phosphoinositide 3 Kinase-Akt."
Phosphorylated AKT binds IRS1 and PIK3CA. 1 / 1
| 1

sparser
"PRR11 silencing also reduced insulin-mediated association of p110α with IRS1 and insulin/IGF-stimulated p-AKT in MCF7 LTED and HCC1428 LTED cells (Fig.  xref and Supplementary Fig.  xref )."