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"Moreover, HRGbeta1 stimulation also promoted a significant decrease in association between IRS-1 and IGF-IR in both the MCF-7 and T47D cells, and densitometric analysis revealed this reduction to be statistically significant in both cell lines (P < = 0.01 (n = 3) and P < = 0.05 (n = 3), respectively)."
trips
"Our findings can be summarized as follows: (i) the tyrosine kinase activity of the IGF-IR is essential for the interaction with p52Shc and IRS-1, (ii) p52Shc and IRS-1 bind to the IGF-IR in the NPEY-juxtamembrane motif, (iii) contrary to p52Shc, IRS-1 binds also to the major autophosphorylation sites (Tyr-1131, -1135, and -1136) of the IGF-IR, and (iv) the amino-terminal domain of p52Shc is required for its association with the IR and the IGF-IR."
sparser
"TRAF4 overexpression further augmented this interaction ( xref A ), indicating that TRAF4 enhances IGF-1-induced tyrosine phosphorylation of IRS-1 through promoting the interaction between IRS-1 and IGF-1R. The amount of p85 bound to IRS-1 upon IGF-1 stimulation also was significantly increased when TRAF4 is overexpressed, consistent with the level of IRS-1 tyrosine phosphorylation."
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"As mentioned previously, another interesting phenomenon noted in these studies is the finding that whilst HRGbeta1 treatment enhanced erbB3-IRS-1 interactions, it also promoted a decrease in the association between IRS-1 and IGF-IR, an effect that was clearly apparent in the MCF-7 and T47D cell lines."
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"Although the K D for IRS1 binding to IGF1R is not well established, the PTB domain of IRS1 has an affinity for INSR phosphosites that is approximately 20-fold weaker than that of SHC1 's PTB domain [XREF_BIBR], and protein copy numbers for IRS1 tended to be two to three orders of magnitude lower than those of SHC1 (XREF_SUPPLEMENTARY)."
sparser
"Altogether, our results demonstrate that TRAF4-mediated IRS-1 ubiquitination leads to the enhancement of IRS-1 tyrosine phosphorylation through promoting the interaction between IRS-1 and IGF-1R; the phosphorylated IRS-1 in turn binds p85 regulatory subunit of PI3K to activate the downstream effectors ( xref )."
sparser
"Although the K D for IRS1 binding to IGF1R is not well-established, the PTB domain of IRS1 has an affinity for INSR phosphosites that is approximately 20-fold weaker than that of SHC1’s PTB domain [ xref ], and protein copy numbers for IRS1 tended to be two to three orders of magnitude lower than those of SHC1 ( xref )."
reach
"Our findings can be summarized as follows : (i) the tyrosine kinase activity of the IGF-IR is essential for the interaction with p52Shc and IRS-1, (ii) p52Shc and IRS-1 bind to the IGF-IR in the NPEY-juxtamembrane motif, (iii) contrary to p52Shc, IRS-1 binds also to the major autophosphorylation sites (Tyr 1131, -1135, and -1136) of the IGF-IR, and (iv) the amino-terminal domain of p52Shc is required for its association with the IR and the IGF-IR."
sparser
"Our findings can be summarized as follows: (i) the tyrosine kinase activity of the IGF-IR is essential for the interaction with p52Shc and IRS-1, (ii) p52Shc and IRS-1 bind to the IGF-IR in the NPEY-juxtamembrane motif, (iii) contrary to p52Shc, IRS-1 binds also to the major autophosphorylation sites (Tyr-1131, -1135, and -1136) of the IGF-IR, and (iv) the amino-terminal domain of p52Shc is required for its association with the IR and the IGF-IR."
sparser
"We further knocked down endogenous TRAF4 in MCF-7 cells and found that TRAF4 depletion abolished IGF-1-induced interaction between IGF-1Rβ and IRS-1; the upregulation of IRS-1 tyrosine phosphorylation, including Y612 and Y896 phosphorylation; and the induced association between p85 and IRS-1 compared with the nontargeting control ( xref D )."
sparser
"Another possibility could be that the K29-linked ubiquitin chain conjugated at the K1186 and K1189 sites stabilizes the binding of IRS-1 and IGF-1R. Although the ubiquitination sites are located at the C-terminal end of IRS-1 while its interaction with IGF-1R occurs at the N-terminal PTB domain ( xref ), the spatial distance between the two regions could be close."
"Ligand binding to the extracellular subunits leads to activation of the intrinsic tyrosine kinases of the transmembrane subunits. The ATP-binding site at Lys1003 and the tyrosine kinase domain are required for all functions of the IGF-IR. Trans-phosphorylation between the subunits involves Tyr1131, 1135 and 1136 in the kinase domain and leads to full activation of kinase activity. Other tyrosine phosphorylated sites serve to recruit specific adaptor molecules via their SH2-binding domains. Phosphorylated Tyr950 in the juxtamembrane region serves as a docking site for the adaptor molecules insulin receptor substrate (IRS)-1 and Shc which are involved in activation of the phosphatidylinositol-3 kinase (PI3K) and MAPK/ERK kinase(MEK)-extracellular-regulated kinase (ERK)signaling pathways, respectively"
sparser
"Indeed, previous studies found that PPP1R12A interacted with insulin receptor substrate 1-insulin-like growth factor 1 receptor (IRS1-IGF1R) complex and mediated the process of IRS1 dephosphorylation, promoting PI3K/AKT cascade activation and in turn led to tumor cell proliferation and tumor growth xref , xref ."
reach
"Collectively, FOXO1 activation is well correlated with Irs1 trafficking defect and the global decrease of Akt2 and highlights Irs1/Akt2/FOXO1 as an additional altered signaling pathway that participates to the early differentiation defect observed in Hrs-KD cells.Akt2 activation during myoblasts differentiation is mediated by IGFR and Irs1 and is regulated by the small GTPase Rab5a that coordinates the recruitment of Irs1 and IGFR on early endosomes [10, 53]."