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phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach
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EGFR affects EGF
18 2 12 6 | 11 1188 845
16 2 12 6 | 11 1053 845
sparser
"We present a model for how high-affinity EGF binding to the EGF receptor may remove the dimerization arm from its intramolecular binding site, thus promoting receptor dimerization and activation."
sparser
"The current data show that GCN4-ICM forms multimers, because the cross-correlation value for this construct,f c = 0.23, is significantly higher than for the dimer control,f c = 0.13, and slightly higher than for EGF-bound EGFR, = 0.19."
sparser
"The EGF binds to high and low affinity sites in EGFR-expressing cells."
reach
"EGF specifically binds to EGFR, promoting formation of either EGFR-EGFR homodimers or EGFR-ErbB-2 heterodimers and allowing the intracellular tyrosine kinase domains to approximate and undergo transautophosphorylation [XREF_BIBR - XREF_BIBR]."
sparser
"EGF binds to extracellular domain of EGFR, whereas gefitinib, a well-known EGFR inhibitor xref , binds to Tyr kinase domain."
reach
"We propose that this dynamic quenching takes place because EGF bound probes interact with tryptophan residues in the extracellular domain of the EGF and EGFR complex."
reach
"A requirement for negative cooperativity is that EGFR dimers bind one EGF."
sparser
"Next in Fig. xref we compared the MC and ODE concentration profiles of EGF bound EGFR monomer in the presence of ligand (160 nM), with a receptor number density of 125 receptors per μm 2 and a low diffusivity of 2 × 10 -15 m 2 s -1 ."
sparser
"Binding of EGF to its receptor, the epidermal growth factor receptor (EGFR), induces dimerization and activation of EGFR ( xref )."
reach
"EGF and EGFR complex translocates to the nucleus."
TGFA binds EGF and EGFR. 10 / 62
| 62
sparser
"Zalutumumab is a fully human IgG1 mAb that targets EGFR domain III and inhibits binding of EGF and TGF-α to EGFR. xref Zalutumumab also prevents conformational changes in EGFR that are necessary for its activation. xref An open-label, randomized, Phase III trial investigated zalutumumab plus best supportive care (BSC) vs BSC alone in 286 patients with R/M HNSCC after failure of platinum-based chemotherapy. xref Zalutumumab prolonged median PFS compared with BSC alone (9.9 vs 8.4 weeks; P =0.0012)."
sparser
"The natural ligands EGF and TGF-α bind to the extracellular domain of EGFR, and activate the receptor and its downstream signal proteins, ultimately causing activation or modulation of various cellular processes [ xref ]."
sparser
"r to demonstrate autocrine stimulation of choriocarcinoma proliferation via a TGF-a-EGFR regulatory loop, we attempted to disrupt EGFR ligand- receptor interactions in JAr cells by culturing them in [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"We also show that the binding of neuregulin-1beta to ErbB4 and ErbB3 and the binding of betacellulin to both ErbB4 and ErbB1 does not decrease at low pH, unlike the binding of epidermal growth factor and transforming growth factor-alpha to ErbB1."
sparser
"10 Lung cancer cells may produce EGFR ligands, such as epidermal growth factor (EGF) and transforming growth factor alpha, which then bind to the EGFR, leading to paracrine and[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Binding of epidermal growth factor (EGF) or transforming growth factor alpha (TGF α ) to the extracellular domain of EGFR produces a number of downstream effects that affect phenotypic cell behavior including proliferation, invasion, metastasis, and inhibition of apoptosis [ xref ]."
sparser
"The EGF-R binds two structurally related ligands, epidermal growth factor (EGF) and transforming growth factor-a (TGF-ct)."
sparser
"Both EGF and TGFα binding to the EGFR lead to endocytosis of EGFR, but receptor-EGF complexes are predominantly trafficked for degradation in lysosomes, while TGFα-bound receptor is predominantly recycled back to the cell surface. xref Thus, changes in ligand-dependent activation can radically impact growth factor receptor signaling."
sparser
"Korc, M.; Chandrasekar, B.; Yamanaka, Y.; Friess, H.; Btichler, M.; Beger, H. G. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increa[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Consistent with this, phosphorylated ERK levels were also unaffected by incubation of cells with an antibody that blocks binding of EGF and TGFα to wild-type EGF receptor (data not shown)."
EGF binds EGFR and GRB2. 10 / 16
2 | 14
sparser
"Upon EGF stimulation, Grb2 binds phosphorylated EGFR and activates the signaling pathway xref , xref ."
sparser
"Together these data indicate that AG-1478 inhibits both constitutive as well as EGF-induced EGFR-Grb2 interaction."
sparser
"Preclinical studies revealed cetuximab could decrease cell proliferation and phosphorylation of EGFR, and blocked the binding of the adaptor protein Grb2 to EGFR upon activation by EGF [ xref ]."
sparser
"Interestingly, in spite of the free phosphonate group with its negative charges, CGP78850 inhibited association of Grb2 with EGFR in intact serum-starved MDA-MB-468 triple-negative breast cancer cells stimulated with EGF in vitro ."
sparser
"Our results support the concept that EGFR interacts with Grb2 in both constitutive and EGF-dependent manners and this interaction is independent of HER3 co-expression."
sparser
"1) Association of Grb2 to EGFR in BxPC-3 induced by EGF in the presence of Erbitux indicates an alternate pathway of Ras-MAPK activation, which may be related with the tumor resistance to treatment; 2) transactivation of EGFR downstream Ras-MAPK pathway by FGF contributes the resistance to treatment; and 3) downregulation of EGFR may increase the response to therapy."
sparser
"Compound inhibited epidermal growth factor (EGF)-induced protein–protein interactions between EGFR (EGF receptor) and Grb2 in MDA-MB-468 cells and inhibited Ras activation in the same cell line."
sparser
"We identified that As 2 O 3 activates EGFR and promotes phosphorylation of p66 ShcA and its interaction with the Grb2 adaptor protein with slower kinetics compared to EGF-mediated EGFR activation."
sparser
"Because Ras activation by EGF involves EGF-stimulated association of EGF-R with Grb2, the EGF-R was immunoprecipitated and a Western blot was probed for Grb2."
sparser
"Pre-clinical studies showed cetuximab decreased cell proliferation and phosphorylation of EGFR, and blocked the binding of the adaptor protein Grb2 to EGFR upon activation by EGF [ xref ]."
EGF binds EGFR and ERBB2. 10 / 15
| 15
sparser
"Additionally, AFM was also applied to investigate the effect of Trastuzumab, as well as Pertuzumab, on HER2-modulated EGF-EGFR interactions, which demonstrated that EGF bound to EGFR more stably in the cells co-expressing EGFR and HER2, and the binding enhancement in the presence of HER2 was inhibited by either Trastuzumab or Pertuzumab [ xref ]."
sparser
"For example, binding of two monomeric ErbB2 proteins to an EGF-induced homodimer of EGFR may cause homodimerization of the ErbB2 molecules followed by their trans-autophosphorylation and consequent ac[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"In this manuscript we demonstrate through combination of scattering spectroscopy, electron microscopy, and generalized multiple particle Mie theory (GMT) simulations that the density- and morphology-dependent spectral response of Au nanoparticle (NP) immunolabels bound to the epidermal growth factor receptors ErbB1 and ErbB2 encodes quantitative information of both the cell surface expression and spatial clustering of the two receptors in different unliganded in vitro cancer cell lines (SKBR3, MCF7, A431)."
sparser
"It is assumed that the mechanism of transactivation involves epidermal growth factor binding to EGFR, followed by transphosphorylation of ErbB2 by the active EGFR kinase."
sparser
"Living-cell single-molecule force spectroscopy (SMFS) combined by Atomic Force Microscopy (AFM) was used by this team of scientists to investigate the effect of two monoclonal antibodies used in cancer therapy, Trastuzumab and Pertuzumab, on HER2-modulated EGF-EGFR interaction, demonstrating the utility of this technique in characterizing the effects of protein-based therapeutics on membrane receptors."
sparser
"Thus, it is possible that two ErbB2 proteins could bind to an EGF-induced homodimer of EGFR resulting in their homodimerization, autophosphorylation and subsequent activation ."
sparser
"Results from co-immunoprecipitation experiments and western blot analyses indicate that tyrosine-phosphorylated ErbB2 and EGFR monomers and stable ErbB2/EGFR high molecular complexes (heterodimers) are formed following EGF stimulation, even if the receptors co-immunoprecipitates also in the absence of the ligand; these data suggest the existence of pre-dimerization inactive receptor clusters on the cell surface."
sparser
"EGF predominantly binds EGFR to induce both EGFR homodimers and EGFRHER2 heterodimers, whereas HRG predominantly binds HER3 and HER4, inducing HER2–HER3 and HER2–HER4 heterodimers."
sparser
"Col IV, LM and FN (but not Col I) adhesion reduce EGF binding to its receptors, EGFR and ErbB2 ( xref )."
sparser
"Exposure of 2 or 20 ug/mL 2C4, a HER2 monoclonal antibody which inhibits HER2-HER3 heterodimerization [ xref ], decreased EGF-dependent HER1-HER2 heterodimer formation with a small concomitant increase in HER1-HER1 homodimerization (Figure xref )."
TGFA binds EGF, EGFR, and AREG. 10 / 12
| 12
sparser
"These include: EGF, TGFα and amphiregulin (AREG), which bind specifically to EGFR; heparin-binding EGF-like growth factor, betacellulin and epiregulin which bind to both EGFR and ErbB4 [ xref ]; and the neuregulins/heregulins (HRGs), which are specific for ErbB3 and ErbB4 [ xref ]."
sparser
"From those ligands, EGF, transforming growth factor alpha and amphiregulin bind specifically to EGFR [ xref ]."
sparser
"EGF, AR and TGFα bind EGFR; HRG, BTC and HB-EGF bind EGFR and erbB-4 ( xref )."
sparser
"EGF, transforming growth factor-alpha and amphiregulin bind exclusively to erbB1[ xref ]."
sparser
"However, only EGF, AREG and TGF-α bind EGFR exclusively; other ligands also bind other ERBB family receptors [ xref , xref , xref ]."
sparser
"The EGF-like ligands include EGF, amphiregulin, and transforming growth factor alpha (TGFα), which only bind to the EGF receptor (EGFR), and heparin binding EGF (HB-EGF), betacellulin, and epiregulin, which bind to both EGFR and ErbB4."
sparser
"TGF-α, amphiregulin, and EGF specifically bind EGFR."
sparser
"EGF, TGF-α and amphiregulin bind specifically to EGFR."
sparser
"Whereas EGF, TGF-α and amphiregulin bind to ErbB1, the heregulins (HRGs; also known as neuregulins) bind ErbB3 and ErbB4 [ xref , xref ]."
sparser
"Epidermal growth factor receptor binds primarily to EGF, transforming growth factor-a, and amphiregulin growth factors, while HER3 and HER4 bind HRG and its isoforms."
EGF binds EGFR and transforming growth factor. 10 / 10
| 10
sparser
"When the EGFR extracellular domain binds to its ligands, such as epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), it forms dimers with other EGFR or other HER family members and undergoes autophosphorylation at the key tyrosine residues, thus activating several downstream signalling pathways such as protein kinase B (AKT/PKB) and mitogen-activated protein kinases (MAPK), which regulate multiple cellular processes, including proliferation, survival and apoptosis."
sparser
"Epidermal growth factor (EGF) and transforming growth factor-α bind directly only to EGFR, whereas neuregulins (also known as heregulins) are specific for ErbB3 and ErbB4 xref , xref ."
sparser
"At least two ligands bind to the EGFR, EGF, and transforming growth factor—α."
sparser
"Extracellular ligands, such as epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), can interact with the EGFR [ xref ], resulting in the stimulation of Akt/PI3K and downstream molecules, including mTOR, eNOS, and the Bcl2-associated antagonist of cell death (BAD)."
sparser
"Nimotuzumab, a recombinant humanized monoclonal immunoglobulin G 1 antibody against human EGFR (HER-1), blocks the binding of epidermal growth factor (EGF) and transforming growth factor-α to EGFR."
sparser
"Ligands such as EGF or transforming growth factor bind to EGFR, which stimulates the tyrosine kinase activity of the receptor."
sparser
"Specific ligands, such as epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), bind to EGFR resulting in receptor dimerization and activation of tyrosine kinase, with receptor auto-phosphorylation and downstream signal transduction. xref – xref Signaling through EGFR has been reported to induce proliferation, invasion, and angiogenesis of tumor cells. xref , xref EGFR is frequently overexpressed in both cell lines and tissues of NSCLC xref – xref and overexpression has been reported to be associated with higher incidence of lymph node metastasis, advanced stage, poor differentiation, and a worse prognosis. xref – xref However, several reports, including a meta-analysis failed to confirm a correlation between overexpression of EGFR and patient outcome. xref , xref In addition, no correlation was found between EGFR expression and tumor response to gefitinib, an EGFR tyrosine kinase inhibitor, in patients with NSCLC. xref Therefore, the clinical significance of EGFR expression in NSCLC is still controversial."
sparser
"The data presented by Doctor Schwab indicated that the anti-epidermal growth factor receptor antibody was no better than C225 for blocking epidermal growth factor/transforming growth factor-α binding [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"When a ligand, such as epidermal growth factor or transforming growth factor-α, binds to EGFR, EGFR dimerizes and a downstream signaling pathway is initiated via the phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways."
sparser
"It has been shown that the overexpression of EGFR is common in ESCC, with an incidence of 50–70%, xref , xref , xref and the overexpression is significantly related to prognosis. xref , xref , xref Nimotuzumab is a recombinant humanized monoclonal IgG1 antibody against human EGFR and blocks the binding of EGF and transforming growth factor‐a to EGFR."
CBL binds EGF and EGFR. 8 / 8
| 8
sparser
"EGF was unable to induce ubiquitination of the serine-mutated EGFR, yet EGF-induced phosphorylation of the c-Cbl-binding site at tyrosine 1045, and c-Cbl-EGFR association, was unaffected."
sparser
"Co-immunoprecipitation studies demonstrated that Cbl became associated with the EGF receptor in an EGF-dependent manner."
sparser
"Further, c-Cbl associates only with EGF-EGFR homodimers, but not with EGF-EGFR/HER2 heterodimers, HER2, HER3, or HER4 ( Levkowitz et al., 1996 ; Muthuswamy et al., 1999 )."
sparser
"A further immuno-coprecipitation assay was conducted to examine the binding of EGFR and c-Cbl and EGF, but not anisomycin, induced the EGFR binding to c-Cbl (D)."
sparser
"Upon EGF binding, EGFR undergoes rapid phosphorylation, internalization and ubiquitination by the E3 ubiquitin ligase Cbl, which targets it for lysosomal degradation [ xref ]."
sparser
"In order to determine the role of c-CBL in differential degradation of EGFR mutants, we assessed EGFR and c-CBL binding, the effect of c-CBL knockdown on steady state levels of EGFR and c-CBL's effect on EGF and erlotinib-induced EGFR degradation (Figure xref )."
sparser
"The EGF-dependent rapid association of Cbl with the autophosphorylated EGF receptor observed in some [46, 49–54, 56, 57] , but not all [55] , studies is apparently mediated by the N-terminal region [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"EGF-induced c-Cbl-EGFR binding was partially inhibited, and receptor ubiquitination was abrogated in cells expressing Y1045F-EGFR."
SRC binds EGF and EGFR. 8 / 8
| 8
sparser
"We previously demonstrated that c-Src directly associates with EGFR upon EGF stimulation and c-Src activation contributes to HNSCC cell invasion ( xref )."
sparser
"This mechanism involves the EGF-dependent association of c-Src with HER1 and phosphorylation of the receptor by c-Src on residues Tyr 845 and Tyr 1101."
sparser
"We have previously reported that c-Src directly associates with EGFR in HNSCC cells upon EGF stimulation ( xref )."
sparser
"EGFR and Src interaction with EGF stimulation were also analyzed by the same method ( xref )."
sparser
"Furthermore, it has been reported that Src directly associates with the epidermal growth factor receptor (EGFR) in OSCC cells upon stimulation with EGF and phosphorylates Crk-associated substrate (Cas), podoplanin acting downstream of Src and Cas to promote cell migration."
sparser
"In experimental systems this synergistic growth requires EGF-dependent association of c-Src with the EGFR and phosphorylation of Tyr-845 of the receptor by c-Src."
sparser
"Significantly, both herbimycin A and PP2 abrogated ouabain-induced but not epidermal growth factor-induced Src binding to the EGFR and the subsequent EGFR tyrosine phosphorylation."
sparser
"We have previously demonstrated that c-Src directly associates with EGFR upon EGF stimulation in HNSCC cells ( xref )."
EGF binds EGFR and AREG. 6 / 6
| 6
sparser
"Inasmuch as we normalized the concentrations of AR and EGF to similar levels of phosphorylation of EGFR, we did not further investigate the stability of AR-EGFR and EGF-EGFR binding in intracellular vesicles."
sparser
"Several ligands, such as EGF and amphiregulin, bind to EGFR, whereas there is no known high-affinity ligand binding to Her-2."
sparser
"For example, Areg and EGF specifically interact with the EGF receptor to promote the growth of normal epithelial cells [ xref ], which may partially explain the prolonged ductal tree extension."
sparser
"Positive regulators of emmprin expression include amphiregulin and EGF-EGFR interactions [ xref ], and negative regulators include Pinin, a nuclear and cell adhesion-related protein [ xref ], and Caveolin-1 which reduces emmprin glycosylation and associated MMP activity [ xref ]."
sparser
"Monoclonal antibodies directed against the EGF receptor show differential bindings of amphiregulin and EGF to the EGF receptor."
sparser
"For example, the concomitant presence of the epidermal growth factor receptor (EGFR) and its ligands EGF and amphiregulin is associated with enhanced tumor aggressiveness and shorter survival in patients. xref K-ras proto-oncogene and mutations of the p53 tumor-suppressor gene and the Smad4 gene are frequently dysregulated in the tumors."
EGF affects EGFR
18 2 12 6 | 11 1188 845
16 2 12 6 | 11 1053 845
sparser
"We present a model for how high-affinity EGF binding to the EGF receptor may remove the dimerization arm from its intramolecular binding site, thus promoting receptor dimerization and activation."
sparser
"The current data show that GCN4-ICM forms multimers, because the cross-correlation value for this construct,f c = 0.23, is significantly higher than for the dimer control,f c = 0.13, and slightly higher than for EGF-bound EGFR, = 0.19."
sparser
"The EGF binds to high and low affinity sites in EGFR-expressing cells."
reach
"EGF specifically binds to EGFR, promoting formation of either EGFR-EGFR homodimers or EGFR-ErbB-2 heterodimers and allowing the intracellular tyrosine kinase domains to approximate and undergo transautophosphorylation [XREF_BIBR - XREF_BIBR]."
sparser
"EGF binds to extracellular domain of EGFR, whereas gefitinib, a well-known EGFR inhibitor xref , binds to Tyr kinase domain."
reach
"We propose that this dynamic quenching takes place because EGF bound probes interact with tryptophan residues in the extracellular domain of the EGF and EGFR complex."
reach
"A requirement for negative cooperativity is that EGFR dimers bind one EGF."
sparser
"Next in Fig. xref we compared the MC and ODE concentration profiles of EGF bound EGFR monomer in the presence of ligand (160 nM), with a receptor number density of 125 receptors per μm 2 and a low diffusivity of 2 × 10 -15 m 2 s -1 ."
sparser
"Binding of EGF to its receptor, the epidermal growth factor receptor (EGFR), induces dimerization and activation of EGFR ( xref )."
reach
"EGF and EGFR complex translocates to the nucleus."
TGFA binds EGF and EGFR. 10 / 62
| 62
sparser
"Zalutumumab is a fully human IgG1 mAb that targets EGFR domain III and inhibits binding of EGF and TGF-α to EGFR. xref Zalutumumab also prevents conformational changes in EGFR that are necessary for its activation. xref An open-label, randomized, Phase III trial investigated zalutumumab plus best supportive care (BSC) vs BSC alone in 286 patients with R/M HNSCC after failure of platinum-based chemotherapy. xref Zalutumumab prolonged median PFS compared with BSC alone (9.9 vs 8.4 weeks; P =0.0012)."
sparser
"The natural ligands EGF and TGF-α bind to the extracellular domain of EGFR, and activate the receptor and its downstream signal proteins, ultimately causing activation or modulation of various cellular processes [ xref ]."
sparser
"r to demonstrate autocrine stimulation of choriocarcinoma proliferation via a TGF-a-EGFR regulatory loop, we attempted to disrupt EGFR ligand- receptor interactions in JAr cells by culturing them in [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"We also show that the binding of neuregulin-1beta to ErbB4 and ErbB3 and the binding of betacellulin to both ErbB4 and ErbB1 does not decrease at low pH, unlike the binding of epidermal growth factor and transforming growth factor-alpha to ErbB1."
sparser
"10 Lung cancer cells may produce EGFR ligands, such as epidermal growth factor (EGF) and transforming growth factor alpha, which then bind to the EGFR, leading to paracrine and[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Binding of epidermal growth factor (EGF) or transforming growth factor alpha (TGF α ) to the extracellular domain of EGFR produces a number of downstream effects that affect phenotypic cell behavior including proliferation, invasion, metastasis, and inhibition of apoptosis [ xref ]."
sparser
"The EGF-R binds two structurally related ligands, epidermal growth factor (EGF) and transforming growth factor-a (TGF-ct)."
sparser
"Both EGF and TGFα binding to the EGFR lead to endocytosis of EGFR, but receptor-EGF complexes are predominantly trafficked for degradation in lysosomes, while TGFα-bound receptor is predominantly recycled back to the cell surface. xref Thus, changes in ligand-dependent activation can radically impact growth factor receptor signaling."
sparser
"Korc, M.; Chandrasekar, B.; Yamanaka, Y.; Friess, H.; Btichler, M.; Beger, H. G. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increa[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Consistent with this, phosphorylated ERK levels were also unaffected by incubation of cells with an antibody that blocks binding of EGF and TGFα to wild-type EGF receptor (data not shown)."
EGF binds EGFR and GRB2. 10 / 16
2 | 14
sparser
"Upon EGF stimulation, Grb2 binds phosphorylated EGFR and activates the signaling pathway xref , xref ."
sparser
"Together these data indicate that AG-1478 inhibits both constitutive as well as EGF-induced EGFR-Grb2 interaction."
sparser
"Preclinical studies revealed cetuximab could decrease cell proliferation and phosphorylation of EGFR, and blocked the binding of the adaptor protein Grb2 to EGFR upon activation by EGF [ xref ]."
sparser
"Interestingly, in spite of the free phosphonate group with its negative charges, CGP78850 inhibited association of Grb2 with EGFR in intact serum-starved MDA-MB-468 triple-negative breast cancer cells stimulated with EGF in vitro ."
sparser
"Our results support the concept that EGFR interacts with Grb2 in both constitutive and EGF-dependent manners and this interaction is independent of HER3 co-expression."
sparser
"1) Association of Grb2 to EGFR in BxPC-3 induced by EGF in the presence of Erbitux indicates an alternate pathway of Ras-MAPK activation, which may be related with the tumor resistance to treatment; 2) transactivation of EGFR downstream Ras-MAPK pathway by FGF contributes the resistance to treatment; and 3) downregulation of EGFR may increase the response to therapy."
sparser
"Compound inhibited epidermal growth factor (EGF)-induced protein–protein interactions between EGFR (EGF receptor) and Grb2 in MDA-MB-468 cells and inhibited Ras activation in the same cell line."
sparser
"We identified that As 2 O 3 activates EGFR and promotes phosphorylation of p66 ShcA and its interaction with the Grb2 adaptor protein with slower kinetics compared to EGF-mediated EGFR activation."
sparser
"Because Ras activation by EGF involves EGF-stimulated association of EGF-R with Grb2, the EGF-R was immunoprecipitated and a Western blot was probed for Grb2."
sparser
"Pre-clinical studies showed cetuximab decreased cell proliferation and phosphorylation of EGFR, and blocked the binding of the adaptor protein Grb2 to EGFR upon activation by EGF [ xref ]."
EGF binds EGFR and ERBB2. 10 / 15
| 15
sparser
"Additionally, AFM was also applied to investigate the effect of Trastuzumab, as well as Pertuzumab, on HER2-modulated EGF-EGFR interactions, which demonstrated that EGF bound to EGFR more stably in the cells co-expressing EGFR and HER2, and the binding enhancement in the presence of HER2 was inhibited by either Trastuzumab or Pertuzumab [ xref ]."
sparser
"For example, binding of two monomeric ErbB2 proteins to an EGF-induced homodimer of EGFR may cause homodimerization of the ErbB2 molecules followed by their trans-autophosphorylation and consequent ac[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"In this manuscript we demonstrate through combination of scattering spectroscopy, electron microscopy, and generalized multiple particle Mie theory (GMT) simulations that the density- and morphology-dependent spectral response of Au nanoparticle (NP) immunolabels bound to the epidermal growth factor receptors ErbB1 and ErbB2 encodes quantitative information of both the cell surface expression and spatial clustering of the two receptors in different unliganded in vitro cancer cell lines (SKBR3, MCF7, A431)."
sparser
"It is assumed that the mechanism of transactivation involves epidermal growth factor binding to EGFR, followed by transphosphorylation of ErbB2 by the active EGFR kinase."
sparser
"Living-cell single-molecule force spectroscopy (SMFS) combined by Atomic Force Microscopy (AFM) was used by this team of scientists to investigate the effect of two monoclonal antibodies used in cancer therapy, Trastuzumab and Pertuzumab, on HER2-modulated EGF-EGFR interaction, demonstrating the utility of this technique in characterizing the effects of protein-based therapeutics on membrane receptors."
sparser
"Thus, it is possible that two ErbB2 proteins could bind to an EGF-induced homodimer of EGFR resulting in their homodimerization, autophosphorylation and subsequent activation ."
sparser
"Results from co-immunoprecipitation experiments and western blot analyses indicate that tyrosine-phosphorylated ErbB2 and EGFR monomers and stable ErbB2/EGFR high molecular complexes (heterodimers) are formed following EGF stimulation, even if the receptors co-immunoprecipitates also in the absence of the ligand; these data suggest the existence of pre-dimerization inactive receptor clusters on the cell surface."
sparser
"EGF predominantly binds EGFR to induce both EGFR homodimers and EGFRHER2 heterodimers, whereas HRG predominantly binds HER3 and HER4, inducing HER2–HER3 and HER2–HER4 heterodimers."
sparser
"Col IV, LM and FN (but not Col I) adhesion reduce EGF binding to its receptors, EGFR and ErbB2 ( xref )."
sparser
"Exposure of 2 or 20 ug/mL 2C4, a HER2 monoclonal antibody which inhibits HER2-HER3 heterodimerization [ xref ], decreased EGF-dependent HER1-HER2 heterodimer formation with a small concomitant increase in HER1-HER1 homodimerization (Figure xref )."
TGFA binds EGF, EGFR, and AREG. 10 / 12
| 12
sparser
"These include: EGF, TGFα and amphiregulin (AREG), which bind specifically to EGFR; heparin-binding EGF-like growth factor, betacellulin and epiregulin which bind to both EGFR and ErbB4 [ xref ]; and the neuregulins/heregulins (HRGs), which are specific for ErbB3 and ErbB4 [ xref ]."
sparser
"From those ligands, EGF, transforming growth factor alpha and amphiregulin bind specifically to EGFR [ xref ]."
sparser
"EGF, AR and TGFα bind EGFR; HRG, BTC and HB-EGF bind EGFR and erbB-4 ( xref )."
sparser
"EGF, transforming growth factor-alpha and amphiregulin bind exclusively to erbB1[ xref ]."
sparser
"However, only EGF, AREG and TGF-α bind EGFR exclusively; other ligands also bind other ERBB family receptors [ xref , xref , xref ]."
sparser
"The EGF-like ligands include EGF, amphiregulin, and transforming growth factor alpha (TGFα), which only bind to the EGF receptor (EGFR), and heparin binding EGF (HB-EGF), betacellulin, and epiregulin, which bind to both EGFR and ErbB4."
sparser
"TGF-α, amphiregulin, and EGF specifically bind EGFR."
sparser
"EGF, TGF-α and amphiregulin bind specifically to EGFR."
sparser
"Whereas EGF, TGF-α and amphiregulin bind to ErbB1, the heregulins (HRGs; also known as neuregulins) bind ErbB3 and ErbB4 [ xref , xref ]."
sparser
"Epidermal growth factor receptor binds primarily to EGF, transforming growth factor-a, and amphiregulin growth factors, while HER3 and HER4 bind HRG and its isoforms."
EGF binds EGFR and transforming growth factor. 10 / 10
| 10
sparser
"When the EGFR extracellular domain binds to its ligands, such as epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), it forms dimers with other EGFR or other HER family members and undergoes autophosphorylation at the key tyrosine residues, thus activating several downstream signalling pathways such as protein kinase B (AKT/PKB) and mitogen-activated protein kinases (MAPK), which regulate multiple cellular processes, including proliferation, survival and apoptosis."
sparser
"Epidermal growth factor (EGF) and transforming growth factor-α bind directly only to EGFR, whereas neuregulins (also known as heregulins) are specific for ErbB3 and ErbB4 xref , xref ."
sparser
"At least two ligands bind to the EGFR, EGF, and transforming growth factor—α."
sparser
"Extracellular ligands, such as epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), can interact with the EGFR [ xref ], resulting in the stimulation of Akt/PI3K and downstream molecules, including mTOR, eNOS, and the Bcl2-associated antagonist of cell death (BAD)."
sparser
"Nimotuzumab, a recombinant humanized monoclonal immunoglobulin G 1 antibody against human EGFR (HER-1), blocks the binding of epidermal growth factor (EGF) and transforming growth factor-α to EGFR."
sparser
"Ligands such as EGF or transforming growth factor bind to EGFR, which stimulates the tyrosine kinase activity of the receptor."
sparser
"Specific ligands, such as epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), bind to EGFR resulting in receptor dimerization and activation of tyrosine kinase, with receptor auto-phosphorylation and downstream signal transduction. xref – xref Signaling through EGFR has been reported to induce proliferation, invasion, and angiogenesis of tumor cells. xref , xref EGFR is frequently overexpressed in both cell lines and tissues of NSCLC xref – xref and overexpression has been reported to be associated with higher incidence of lymph node metastasis, advanced stage, poor differentiation, and a worse prognosis. xref – xref However, several reports, including a meta-analysis failed to confirm a correlation between overexpression of EGFR and patient outcome. xref , xref In addition, no correlation was found between EGFR expression and tumor response to gefitinib, an EGFR tyrosine kinase inhibitor, in patients with NSCLC. xref Therefore, the clinical significance of EGFR expression in NSCLC is still controversial."
sparser
"The data presented by Doctor Schwab indicated that the anti-epidermal growth factor receptor antibody was no better than C225 for blocking epidermal growth factor/transforming growth factor-α binding [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"When a ligand, such as epidermal growth factor or transforming growth factor-α, binds to EGFR, EGFR dimerizes and a downstream signaling pathway is initiated via the phosphoinositide 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways."
sparser
"It has been shown that the overexpression of EGFR is common in ESCC, with an incidence of 50–70%, xref , xref , xref and the overexpression is significantly related to prognosis. xref , xref , xref Nimotuzumab is a recombinant humanized monoclonal IgG1 antibody against human EGFR and blocks the binding of EGF and transforming growth factor‐a to EGFR."
CBL binds EGF and EGFR. 8 / 8
| 8
sparser
"EGF was unable to induce ubiquitination of the serine-mutated EGFR, yet EGF-induced phosphorylation of the c-Cbl-binding site at tyrosine 1045, and c-Cbl-EGFR association, was unaffected."
sparser
"Co-immunoprecipitation studies demonstrated that Cbl became associated with the EGF receptor in an EGF-dependent manner."
sparser
"Further, c-Cbl associates only with EGF-EGFR homodimers, but not with EGF-EGFR/HER2 heterodimers, HER2, HER3, or HER4 ( Levkowitz et al., 1996 ; Muthuswamy et al., 1999 )."
sparser
"A further immuno-coprecipitation assay was conducted to examine the binding of EGFR and c-Cbl and EGF, but not anisomycin, induced the EGFR binding to c-Cbl (D)."
sparser
"Upon EGF binding, EGFR undergoes rapid phosphorylation, internalization and ubiquitination by the E3 ubiquitin ligase Cbl, which targets it for lysosomal degradation [ xref ]."
sparser
"In order to determine the role of c-CBL in differential degradation of EGFR mutants, we assessed EGFR and c-CBL binding, the effect of c-CBL knockdown on steady state levels of EGFR and c-CBL's effect on EGF and erlotinib-induced EGFR degradation (Figure xref )."
sparser
"The EGF-dependent rapid association of Cbl with the autophosphorylated EGF receptor observed in some [46, 49–54, 56, 57] , but not all [55] , studies is apparently mediated by the N-terminal region [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"EGF-induced c-Cbl-EGFR binding was partially inhibited, and receptor ubiquitination was abrogated in cells expressing Y1045F-EGFR."
SRC binds EGF and EGFR. 8 / 8
| 8
sparser
"We previously demonstrated that c-Src directly associates with EGFR upon EGF stimulation and c-Src activation contributes to HNSCC cell invasion ( xref )."
sparser
"This mechanism involves the EGF-dependent association of c-Src with HER1 and phosphorylation of the receptor by c-Src on residues Tyr 845 and Tyr 1101."
sparser
"We have previously reported that c-Src directly associates with EGFR in HNSCC cells upon EGF stimulation ( xref )."
sparser
"EGFR and Src interaction with EGF stimulation were also analyzed by the same method ( xref )."
sparser
"Furthermore, it has been reported that Src directly associates with the epidermal growth factor receptor (EGFR) in OSCC cells upon stimulation with EGF and phosphorylates Crk-associated substrate (Cas), podoplanin acting downstream of Src and Cas to promote cell migration."
sparser
"In experimental systems this synergistic growth requires EGF-dependent association of c-Src with the EGFR and phosphorylation of Tyr-845 of the receptor by c-Src."
sparser
"Significantly, both herbimycin A and PP2 abrogated ouabain-induced but not epidermal growth factor-induced Src binding to the EGFR and the subsequent EGFR tyrosine phosphorylation."
sparser
"We have previously demonstrated that c-Src directly associates with EGFR upon EGF stimulation in HNSCC cells ( xref )."
EGF binds EGFR and AREG. 6 / 6
| 6
sparser
"Inasmuch as we normalized the concentrations of AR and EGF to similar levels of phosphorylation of EGFR, we did not further investigate the stability of AR-EGFR and EGF-EGFR binding in intracellular vesicles."
sparser
"Several ligands, such as EGF and amphiregulin, bind to EGFR, whereas there is no known high-affinity ligand binding to Her-2."
sparser
"For example, Areg and EGF specifically interact with the EGF receptor to promote the growth of normal epithelial cells [ xref ], which may partially explain the prolonged ductal tree extension."
sparser
"Positive regulators of emmprin expression include amphiregulin and EGF-EGFR interactions [ xref ], and negative regulators include Pinin, a nuclear and cell adhesion-related protein [ xref ], and Caveolin-1 which reduces emmprin glycosylation and associated MMP activity [ xref ]."
sparser
"Monoclonal antibodies directed against the EGF receptor show differential bindings of amphiregulin and EGF to the EGF receptor."
sparser
"For example, the concomitant presence of the epidermal growth factor receptor (EGFR) and its ligands EGF and amphiregulin is associated with enhanced tumor aggressiveness and shorter survival in patients. xref K-ras proto-oncogene and mutations of the p53 tumor-suppressor gene and the Smad4 gene are frequently dysregulated in the tumors."
ERBB2 affects EGFR
14 32 3 12 6 | 595 599
14 32 3 12 6 | 464 598
sparser
"The absence or low expression of ErbB-1 in meningiomas may preclude formation of ErbB-1 and ErbB-2 heterodimers."
reach
"Interestingly, Tanizaki et al. revealed differential functional consequences in a cell line that overexpresses c-Met upon heterodimerization between c-Met and RET, EGFR, Her2 or Her3 [XREF_BIBR]."
reach
"It is most likely that ErbB2 forms a heterodimer with EGFR, although a role for ErbB3 and ErbB4 can not be excluded."
sparser
"miR-217 inhibitor induced interactions of CAGE with EGFR and HER2 in Malme3M cells."
sparser
"HER3 acts as a signal-promoting molecule via its interactions with HER2 and EGFR, as described above."
reach
"HRG-alpha activated tyrosine phosphorylation of epidermal growth factor receptor (EGFR), erbB2, and erbB3 and induced not only erbB3 and erbB2 but also erbB3 and EGFR and erbB2 and EGFR heterodimer formation in MKN-28 cancer cells."
reach
"In addition, ERBB1 and ERBB2 heterodimers are in the minority."
sparser
"In particular, Arg228 of EGFR interacted stably with Glu243 of Her2 through a salt bridge in our simulations of the ligand-bound EGFRHer2 heterodimer ( xref )."
reach
"Dynamics of the dimer interfaces in the EGFR and Her2 heterodimer and Her2 homodimer."
sparser
"Concurrent binding was also seen when biotinylated forms of HER2 and EGFR antigens were immobilized on separate streptavidin biosensors and then sequentially exposed to the DuetMab and the other antigen ( xref )."
| 67
sparser
"We have used SPR analysis, Western blot, and PathHunter assay to show that the compound 5 binds specifically to HER2 domain IV and disrupts the protein-protein interactions of EGFR-HER2 as well as HER2HER3."
sparser
"High-grade dysplasia (HGD) was associated with overexpression of HER1 (20.7% vs. 3.1%, p = 0.023), HER2 (5.3% vs. 0.0%, p = 0.187) and HER3 (47.4% vs. 9.4%, p<0.001) compared to low-grade dysplasia (LGD)."
sparser
"The EGFR also interacts with its three known homologues, ErbB2 (also called Neu or HER2), ErbB3 (HER3), and ErbB4 (HER4), in a ligand-dependent fashion to form heterodimers [3,17] ."
sparser
"Examples of IHC staining for total and phosphorylated forms of EGFR, HER2 and HER3 are shown in xref ."
sparser
"According to previous research, overexpression of EGFR, ERBB2, and ERBB3 is associated with poor prognosis and negatively correlated with estrogen receptor (ER) expression in breast cancer [ xref , xref ]."
sparser
"In view of these observations and the fact that multiple signaling pathways, including EGFRs and IGF-1R, are dysregulated in colorectal cancer, we examined the constitutive levels of total and the activated (tyrosine phosphorylation) forms of EGFR, HER-2, and HER-3 as well as the activation of IGF-1R in response to curcumin and/or resveratrol."
sparser
"The close cooperativity of EGFR with Her2 has led to the development of other ErbB receptor family inhibitor drugs including the dual EGFR/HER2 TKI lapatinib and therapeutic antibody, pertuzumab, which blocks Her2 interactions with EGFR and Her3."
sparser
"Thus, we next examined the binding of trastuzumab to HER2, EGFR and HER3."
sparser
"If we assume that the PPI interaction site of HER2 is similar to that of EGFR, we can propose that compound 21 binds to the pocket of HER2 PPI site in domain IV and thus inhibits protein-protein interactions of HER3-HER2 as well as EGFR-HER2, hence inhibiting the signaling for cell growth."
sparser
"In fact, HER-3 expression or signaling is associated with resistance to HER-2 inhibitors in HER-2-amplified breast cancers [ xref ], EGFR inhibitors in lung cancers [ xref ], pertuzumab in ovarian cancers [ xref ], antiestrogen therapies in ER-positive breast cancers [ xref – xref ], EGFR inhibitors in head and neck cancer [ xref ] and hormone therapies in prostate cancers [ xref ]."
| 21
sparser
"Neratinib is a third-generation orally available ERBB1/2/4 inhibitor that irreversibly binds to ERBB1, ERBB2 and ERBB4."
sparser
"The calculated MM/GBSA binding free energies for Saquinavir are -8.51, -10.12 and -9.37 kcal/mol when bound to EGFR, ErbB2 and ErbB4, respectively and -1.11, -1.68 and -2.51 kcal/mol, respectively, for Indinavir."
sparser
"In this way, activation of this receptor is achieved only through the formation of heterodimers with EGFR, ERBB2 or ERBB4 [ xref – xref ]."
sparser
"Afatinib is an irreversible ErbB family blocker that covalently binds to EGFR, HER2 and HER4, and inhibits signalling from all ErbB family homo- and heterodimers ( xref ; xref )."
sparser
"In addition to gefitinib and erlotinib, a second-generation EGFR/HER-TKI afatinib is approved as a first-line treatment for the advanced NSCLC harboring act EGFR m in the US, Europe, Taiwan, Japan, and other countries. xref Afatinib is an ATP-competitive aniline-quinazoline derivate containing a reactive acrylamide group, covalently binding to EGFR, HER2, and HER4 and irreversibly inhibiting HER-family phosphorylation and signal transduction. xref The theoretical advantages and promising preclinical data indicated that afatinib irreversibly inhibited the enzymatic activation of wt EGFR , EGFR L858R , EGFR L858R/T790M , EGFR L858R/T854A , wt HER2 , HER2 amplification, and wt HER4 , as well as showed antitumor activities in both EGFR/HER-TKI-naive and resistant tumor cells and xenograft models. xref , xref "
sparser
"Dacomitinib binds irreversibly to EGFR, Her2 and Her4."
sparser
"Afatinib binds to EGFR, HER2 and HER4, irreversibly inhibiting tyrosine kinase autophosphorylation; it also inhibits transphosphorylation of HER3."
sparser
"Since HER3 lacks intrinsic kinase activity, induction of signal occurs through formation of Heterodimers with EGFR, HER2 and HER4 ( xref )."
sparser
"Since ERBB3 lacks intrinsic kinase activity, signal transduction occurs through formation of heterodimers with EGFR, ERBB2, and ERBB4."
sparser
"Afatinib covalently binds to EGFR, HER2, and ErbB4 [ xref ]."
EGF binds EGFR and ERBB2. 10 / 15
| 15
sparser
"Additionally, AFM was also applied to investigate the effect of Trastuzumab, as well as Pertuzumab, on HER2-modulated EGF-EGFR interactions, which demonstrated that EGF bound to EGFR more stably in the cells co-expressing EGFR and HER2, and the binding enhancement in the presence of HER2 was inhibited by either Trastuzumab or Pertuzumab [ xref ]."
sparser
"For example, binding of two monomeric ErbB2 proteins to an EGF-induced homodimer of EGFR may cause homodimerization of the ErbB2 molecules followed by their trans-autophosphorylation and consequent ac[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"In this manuscript we demonstrate through combination of scattering spectroscopy, electron microscopy, and generalized multiple particle Mie theory (GMT) simulations that the density- and morphology-dependent spectral response of Au nanoparticle (NP) immunolabels bound to the epidermal growth factor receptors ErbB1 and ErbB2 encodes quantitative information of both the cell surface expression and spatial clustering of the two receptors in different unliganded in vitro cancer cell lines (SKBR3, MCF7, A431)."
sparser
"It is assumed that the mechanism of transactivation involves epidermal growth factor binding to EGFR, followed by transphosphorylation of ErbB2 by the active EGFR kinase."
sparser
"Living-cell single-molecule force spectroscopy (SMFS) combined by Atomic Force Microscopy (AFM) was used by this team of scientists to investigate the effect of two monoclonal antibodies used in cancer therapy, Trastuzumab and Pertuzumab, on HER2-modulated EGF-EGFR interaction, demonstrating the utility of this technique in characterizing the effects of protein-based therapeutics on membrane receptors."
sparser
"Thus, it is possible that two ErbB2 proteins could bind to an EGF-induced homodimer of EGFR resulting in their homodimerization, autophosphorylation and subsequent activation ."
sparser
"Results from co-immunoprecipitation experiments and western blot analyses indicate that tyrosine-phosphorylated ErbB2 and EGFR monomers and stable ErbB2/EGFR high molecular complexes (heterodimers) are formed following EGF stimulation, even if the receptors co-immunoprecipitates also in the absence of the ligand; these data suggest the existence of pre-dimerization inactive receptor clusters on the cell surface."
sparser
"EGF predominantly binds EGFR to induce both EGFR homodimers and EGFRHER2 heterodimers, whereas HRG predominantly binds HER3 and HER4, inducing HER2–HER3 and HER2–HER4 heterodimers."
sparser
"Col IV, LM and FN (but not Col I) adhesion reduce EGF binding to its receptors, EGFR and ErbB2 ( xref )."
sparser
"Exposure of 2 or 20 ug/mL 2C4, a HER2 monoclonal antibody which inhibits HER2-HER3 heterodimerization [ xref ], decreased EGF-dependent HER1-HER2 heterodimer formation with a small concomitant increase in HER1-HER1 homodimerization (Figure xref )."
| 15
sparser
"Afatinib covalently binds to all homodimers and heterodimers formed by EGFR, HER2, ErbB3 and ErbB4, thereby inhibiting tyrosine kinase autophosphorylation and downregulating ErbB signalling [ xref – xref ]."
sparser
"Afatinib is an irreversible ErbB-family inhibitor that, by contrast with EGFR tyrosine kinase inhibitors, selectively blocks signalling from all homodimers and heterodimers formed by EGFR, HER2, HER3,[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Overexpression of EGFR, erbB2, erbB3 or erbB4 alone was not significantly associated with a shortened survival."
sparser
"HER2 forms heterodimers with HER1, HER3, or HER4, generating signals that cause cell growth, overproliferation, and migration."
sparser
"Pertuzumab, another monoclonal antibody, is a HER2 dimerization inhibitor that binds to a different epitope on HER2 than trastuzumab and inhibits HER2 dimer formation with HER1, HER3, and HER4, which is required for HER2 to engender a signal ( xref )."
sparser
"HER2 can form a heterodimer with EGFR, HER3 or HER4 and is often over-expressed in breast cancer [ xref ]."
sparser
"However, it is unclear how erbB2 specifically associates with erbB1, erbB3, or erbB4 in the presence of particular ligands."
sparser
"The total receptors HER1, HER2, HER3, and HER4 were significantly associated with standard prognostic factors in two instances."
sparser
"EGFR, HER3 and HER4 but not HER2 are associated with penile carcinogenesis."
sparser
"This included several genes commonly associated with cancer pathogenesis such as the EGF receptor family members ERBB2, ERBB3, and ERBB4 , the purported melanoma oncogenes MITF and NEDD9 , and several markers of pluripotency, including NES, SOX2, and NANOG ( xref )."
EFNB1 binds EGFR and ERBB2. 8 / 8
| 7 1
sparser
"The data suggest that EFNB1 associates with ERBB1 and ERBB2 (alone or in combination) and that PTPN13 modulates these interactions by regulating EFNB1 phosphorylation and downstream signaling."
sparser
"EFNB1 associates with ERBB1 and ERBB2."
sparser
"Here we report that, like ERBB2, ERBB1 associates with EFNB1."
reach
"Both of these BL breast cancer cell lines demonstrate over-expression of ErbB1 XREF_BIBR, XREF_BIBR suggesting that ErbB1 may hetero-dimerize with low levels of endogenous ErbB2 (forming an ErbB1, ErbB2, and EphrinB1 complex) and mediate signaling from the complex."
sparser
"Consistent with our previous studies, ERBB1 and ERBB2 associate with EFNB1 in both cell types ( xref )."
sparser
"Given that EFNB1 associates with ERBB1 and ERBB2, we wondered whether treatment with targeted drugs mediates changes in partner associations within these complexes that might account for sustained signaling in the presence of drug."
sparser
"These data show that ERBB1 and ERBB2 associate with EFNB1 in primary human tonsil cells as well as those expressing HPV oncogenes."
sparser
"Our data suggest that PTPN13 modulates EFNB1-mediated signaling and that EFNB1 associates with ERBB1 and ERBB2."
EGFR binds ERBB2 and ESR1. 6 / 6
| 6
sparser
"For example, concomitant over-expressions of the genes ERα36, EGFR and HER2 were strongly associated with aggressive forms (e.g. lymph node metastasis and high staging) of papillary thyroid carcinoma[ xref ]."
sparser
"It is well established that in ER-positive breast tumors, overexpression of EGFR and/or HER2 is associated with resistance to endocrine therapy ( xref - xref )."
sparser
"We hypothesize that direct interaction of the HER tyrosine kinases with the ER leads to the ER activation and is involved in the compensatory targeted therapy resistance mechanisms."
sparser
"Concomitant high expression of ERα36, EGFR and HER2 was strongly associated with aggressive behaviors including extrathyroidal extension (ETE), lymph node metastasis (LNM) and high TNM stage in PTCs (P < 0.001)."
sparser
"The docked complexes involving ESR1-EGFR and Erbb2 shown in Figure xref , Figure xref and Figure xref revealed that ESR1-EGFR and ESR1-Erbb2 interactions are mutually exclusive because of shared binding sites of the interacting proteins, and hence EGFR and Erbb2 cannot bind to ESR1 at the same time (see additional files xref , xref , xref )."
sparser
"It is now well established that in ER-positive primary breast cancers, overexpression of both EGFR and HER2 is associated with resistance to endocrine therapy ( xref – xref )."
EGFR affects ERBB2
14 32 3 12 6 | 595 599
14 32 3 12 6 | 464 598
sparser
"The absence or low expression of ErbB-1 in meningiomas may preclude formation of ErbB-1 and ErbB-2 heterodimers."
reach
"Interestingly, Tanizaki et al. revealed differential functional consequences in a cell line that overexpresses c-Met upon heterodimerization between c-Met and RET, EGFR, Her2 or Her3 [XREF_BIBR]."
reach
"It is most likely that ErbB2 forms a heterodimer with EGFR, although a role for ErbB3 and ErbB4 can not be excluded."
sparser
"miR-217 inhibitor induced interactions of CAGE with EGFR and HER2 in Malme3M cells."
sparser
"HER3 acts as a signal-promoting molecule via its interactions with HER2 and EGFR, as described above."
reach
"HRG-alpha activated tyrosine phosphorylation of epidermal growth factor receptor (EGFR), erbB2, and erbB3 and induced not only erbB3 and erbB2 but also erbB3 and EGFR and erbB2 and EGFR heterodimer formation in MKN-28 cancer cells."
reach
"In addition, ERBB1 and ERBB2 heterodimers are in the minority."
sparser
"In particular, Arg228 of EGFR interacted stably with Glu243 of Her2 through a salt bridge in our simulations of the ligand-bound EGFRHer2 heterodimer ( xref )."
reach
"Dynamics of the dimer interfaces in the EGFR and Her2 heterodimer and Her2 homodimer."
sparser
"Concurrent binding was also seen when biotinylated forms of HER2 and EGFR antigens were immobilized on separate streptavidin biosensors and then sequentially exposed to the DuetMab and the other antigen ( xref )."
| 67
sparser
"We have used SPR analysis, Western blot, and PathHunter assay to show that the compound 5 binds specifically to HER2 domain IV and disrupts the protein-protein interactions of EGFR-HER2 as well as HER2HER3."
sparser
"High-grade dysplasia (HGD) was associated with overexpression of HER1 (20.7% vs. 3.1%, p = 0.023), HER2 (5.3% vs. 0.0%, p = 0.187) and HER3 (47.4% vs. 9.4%, p<0.001) compared to low-grade dysplasia (LGD)."
sparser
"The EGFR also interacts with its three known homologues, ErbB2 (also called Neu or HER2), ErbB3 (HER3), and ErbB4 (HER4), in a ligand-dependent fashion to form heterodimers [3,17] ."
sparser
"Examples of IHC staining for total and phosphorylated forms of EGFR, HER2 and HER3 are shown in xref ."
sparser
"According to previous research, overexpression of EGFR, ERBB2, and ERBB3 is associated with poor prognosis and negatively correlated with estrogen receptor (ER) expression in breast cancer [ xref , xref ]."
sparser
"In view of these observations and the fact that multiple signaling pathways, including EGFRs and IGF-1R, are dysregulated in colorectal cancer, we examined the constitutive levels of total and the activated (tyrosine phosphorylation) forms of EGFR, HER-2, and HER-3 as well as the activation of IGF-1R in response to curcumin and/or resveratrol."
sparser
"The close cooperativity of EGFR with Her2 has led to the development of other ErbB receptor family inhibitor drugs including the dual EGFR/HER2 TKI lapatinib and therapeutic antibody, pertuzumab, which blocks Her2 interactions with EGFR and Her3."
sparser
"Thus, we next examined the binding of trastuzumab to HER2, EGFR and HER3."
sparser
"If we assume that the PPI interaction site of HER2 is similar to that of EGFR, we can propose that compound 21 binds to the pocket of HER2 PPI site in domain IV and thus inhibits protein-protein interactions of HER3-HER2 as well as EGFR-HER2, hence inhibiting the signaling for cell growth."
sparser
"In fact, HER-3 expression or signaling is associated with resistance to HER-2 inhibitors in HER-2-amplified breast cancers [ xref ], EGFR inhibitors in lung cancers [ xref ], pertuzumab in ovarian cancers [ xref ], antiestrogen therapies in ER-positive breast cancers [ xref – xref ], EGFR inhibitors in head and neck cancer [ xref ] and hormone therapies in prostate cancers [ xref ]."
| 21
sparser
"Neratinib is a third-generation orally available ERBB1/2/4 inhibitor that irreversibly binds to ERBB1, ERBB2 and ERBB4."
sparser
"The calculated MM/GBSA binding free energies for Saquinavir are -8.51, -10.12 and -9.37 kcal/mol when bound to EGFR, ErbB2 and ErbB4, respectively and -1.11, -1.68 and -2.51 kcal/mol, respectively, for Indinavir."
sparser
"In this way, activation of this receptor is achieved only through the formation of heterodimers with EGFR, ERBB2 or ERBB4 [ xref – xref ]."
sparser
"Afatinib is an irreversible ErbB family blocker that covalently binds to EGFR, HER2 and HER4, and inhibits signalling from all ErbB family homo- and heterodimers ( xref ; xref )."
sparser
"In addition to gefitinib and erlotinib, a second-generation EGFR/HER-TKI afatinib is approved as a first-line treatment for the advanced NSCLC harboring act EGFR m in the US, Europe, Taiwan, Japan, and other countries. xref Afatinib is an ATP-competitive aniline-quinazoline derivate containing a reactive acrylamide group, covalently binding to EGFR, HER2, and HER4 and irreversibly inhibiting HER-family phosphorylation and signal transduction. xref The theoretical advantages and promising preclinical data indicated that afatinib irreversibly inhibited the enzymatic activation of wt EGFR , EGFR L858R , EGFR L858R/T790M , EGFR L858R/T854A , wt HER2 , HER2 amplification, and wt HER4 , as well as showed antitumor activities in both EGFR/HER-TKI-naive and resistant tumor cells and xenograft models. xref , xref "
sparser
"Dacomitinib binds irreversibly to EGFR, Her2 and Her4."
sparser
"Afatinib binds to EGFR, HER2 and HER4, irreversibly inhibiting tyrosine kinase autophosphorylation; it also inhibits transphosphorylation of HER3."
sparser
"Since HER3 lacks intrinsic kinase activity, induction of signal occurs through formation of Heterodimers with EGFR, HER2 and HER4 ( xref )."
sparser
"Since ERBB3 lacks intrinsic kinase activity, signal transduction occurs through formation of heterodimers with EGFR, ERBB2, and ERBB4."
sparser
"Afatinib covalently binds to EGFR, HER2, and ErbB4 [ xref ]."
EGF binds EGFR and ERBB2. 10 / 15
| 15
sparser
"Additionally, AFM was also applied to investigate the effect of Trastuzumab, as well as Pertuzumab, on HER2-modulated EGF-EGFR interactions, which demonstrated that EGF bound to EGFR more stably in the cells co-expressing EGFR and HER2, and the binding enhancement in the presence of HER2 was inhibited by either Trastuzumab or Pertuzumab [ xref ]."
sparser
"For example, binding of two monomeric ErbB2 proteins to an EGF-induced homodimer of EGFR may cause homodimerization of the ErbB2 molecules followed by their trans-autophosphorylation and consequent ac[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"In this manuscript we demonstrate through combination of scattering spectroscopy, electron microscopy, and generalized multiple particle Mie theory (GMT) simulations that the density- and morphology-dependent spectral response of Au nanoparticle (NP) immunolabels bound to the epidermal growth factor receptors ErbB1 and ErbB2 encodes quantitative information of both the cell surface expression and spatial clustering of the two receptors in different unliganded in vitro cancer cell lines (SKBR3, MCF7, A431)."
sparser
"It is assumed that the mechanism of transactivation involves epidermal growth factor binding to EGFR, followed by transphosphorylation of ErbB2 by the active EGFR kinase."
sparser
"Living-cell single-molecule force spectroscopy (SMFS) combined by Atomic Force Microscopy (AFM) was used by this team of scientists to investigate the effect of two monoclonal antibodies used in cancer therapy, Trastuzumab and Pertuzumab, on HER2-modulated EGF-EGFR interaction, demonstrating the utility of this technique in characterizing the effects of protein-based therapeutics on membrane receptors."
sparser
"Thus, it is possible that two ErbB2 proteins could bind to an EGF-induced homodimer of EGFR resulting in their homodimerization, autophosphorylation and subsequent activation ."
sparser
"Results from co-immunoprecipitation experiments and western blot analyses indicate that tyrosine-phosphorylated ErbB2 and EGFR monomers and stable ErbB2/EGFR high molecular complexes (heterodimers) are formed following EGF stimulation, even if the receptors co-immunoprecipitates also in the absence of the ligand; these data suggest the existence of pre-dimerization inactive receptor clusters on the cell surface."
sparser
"EGF predominantly binds EGFR to induce both EGFR homodimers and EGFRHER2 heterodimers, whereas HRG predominantly binds HER3 and HER4, inducing HER2–HER3 and HER2–HER4 heterodimers."
sparser
"Col IV, LM and FN (but not Col I) adhesion reduce EGF binding to its receptors, EGFR and ErbB2 ( xref )."
sparser
"Exposure of 2 or 20 ug/mL 2C4, a HER2 monoclonal antibody which inhibits HER2-HER3 heterodimerization [ xref ], decreased EGF-dependent HER1-HER2 heterodimer formation with a small concomitant increase in HER1-HER1 homodimerization (Figure xref )."
| 15
sparser
"Afatinib covalently binds to all homodimers and heterodimers formed by EGFR, HER2, ErbB3 and ErbB4, thereby inhibiting tyrosine kinase autophosphorylation and downregulating ErbB signalling [ xref – xref ]."
sparser
"Afatinib is an irreversible ErbB-family inhibitor that, by contrast with EGFR tyrosine kinase inhibitors, selectively blocks signalling from all homodimers and heterodimers formed by EGFR, HER2, HER3,[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Overexpression of EGFR, erbB2, erbB3 or erbB4 alone was not significantly associated with a shortened survival."
sparser
"HER2 forms heterodimers with HER1, HER3, or HER4, generating signals that cause cell growth, overproliferation, and migration."
sparser
"Pertuzumab, another monoclonal antibody, is a HER2 dimerization inhibitor that binds to a different epitope on HER2 than trastuzumab and inhibits HER2 dimer formation with HER1, HER3, and HER4, which is required for HER2 to engender a signal ( xref )."
sparser
"HER2 can form a heterodimer with EGFR, HER3 or HER4 and is often over-expressed in breast cancer [ xref ]."
sparser
"However, it is unclear how erbB2 specifically associates with erbB1, erbB3, or erbB4 in the presence of particular ligands."
sparser
"The total receptors HER1, HER2, HER3, and HER4 were significantly associated with standard prognostic factors in two instances."
sparser
"EGFR, HER3 and HER4 but not HER2 are associated with penile carcinogenesis."
sparser
"This included several genes commonly associated with cancer pathogenesis such as the EGF receptor family members ERBB2, ERBB3, and ERBB4 , the purported melanoma oncogenes MITF and NEDD9 , and several markers of pluripotency, including NES, SOX2, and NANOG ( xref )."
EFNB1 binds EGFR and ERBB2. 8 / 8
| 7 1
sparser
"The data suggest that EFNB1 associates with ERBB1 and ERBB2 (alone or in combination) and that PTPN13 modulates these interactions by regulating EFNB1 phosphorylation and downstream signaling."
sparser
"EFNB1 associates with ERBB1 and ERBB2."
sparser
"Here we report that, like ERBB2, ERBB1 associates with EFNB1."
reach
"Both of these BL breast cancer cell lines demonstrate over-expression of ErbB1 XREF_BIBR, XREF_BIBR suggesting that ErbB1 may hetero-dimerize with low levels of endogenous ErbB2 (forming an ErbB1, ErbB2, and EphrinB1 complex) and mediate signaling from the complex."
sparser
"Consistent with our previous studies, ERBB1 and ERBB2 associate with EFNB1 in both cell types ( xref )."
sparser
"Given that EFNB1 associates with ERBB1 and ERBB2, we wondered whether treatment with targeted drugs mediates changes in partner associations within these complexes that might account for sustained signaling in the presence of drug."
sparser
"These data show that ERBB1 and ERBB2 associate with EFNB1 in primary human tonsil cells as well as those expressing HPV oncogenes."
sparser
"Our data suggest that PTPN13 modulates EFNB1-mediated signaling and that EFNB1 associates with ERBB1 and ERBB2."
EGFR binds ERBB2 and ESR1. 6 / 6
| 6
sparser
"For example, concomitant over-expressions of the genes ERα36, EGFR and HER2 were strongly associated with aggressive forms (e.g. lymph node metastasis and high staging) of papillary thyroid carcinoma[ xref ]."
sparser
"It is well established that in ER-positive breast tumors, overexpression of EGFR and/or HER2 is associated with resistance to endocrine therapy ( xref - xref )."
sparser
"We hypothesize that direct interaction of the HER tyrosine kinases with the ER leads to the ER activation and is involved in the compensatory targeted therapy resistance mechanisms."
sparser
"Concomitant high expression of ERα36, EGFR and HER2 was strongly associated with aggressive behaviors including extrathyroidal extension (ETE), lymph node metastasis (LNM) and high TNM stage in PTCs (P < 0.001)."
sparser
"The docked complexes involving ESR1-EGFR and Erbb2 shown in Figure xref , Figure xref and Figure xref revealed that ESR1-EGFR and ESR1-Erbb2 interactions are mutually exclusive because of shared binding sites of the interacting proteins, and hence EGFR and Erbb2 cannot bind to ESR1 at the same time (see additional files xref , xref , xref )."
sparser
"It is now well established that in ER-positive primary breast cancers, overexpression of both EGFR and HER2 is associated with resistance to endocrine therapy ( xref – xref )."
EGFR affects CBL
2 95 10 | 11 236 141
2 95 10 | 11 192 139
biogrid
No evidence text available
reach
"The 16E5 effect on EGFR levels was similar to that seen by proteosomal inhibition, suggesting that interfering with the EGFR and c-Cbl interaction was an important contributor to E5 activation of EGFR."
sparser
"Therefore, we conclude that direct interaction between Cbl and EGFR may not be necessary for ligand-receptor endocytosis in vertebrate and invertebrate cells."
sparser
"Cdc42 is proposed to function in a positive feedback loop with the EGFR whereby epidermal growth factor (EGF) stimulates activation of Cdc42 and its interaction with specific target proteins: Cdc42, in turn, inhibits EGFR degradation by preventing binding of c-Cbl to EGFR."
sparser
"To test binding of Cbl proteins to EGFR, we prepared whole lysates from EGF-stimulated A-431 cells and incubated them for 1 hr at 4°C with immobilized GST–Cbl proteins."
sparser
"Other proteins that are capable of binding to Cbl and/or EGFR and implicated in the regulation of EGFR internalization and degradation are: Alix [ xref ], c-Abl tyrosine kinase [ xref ], Sts1/TULA2 [ xref ], Lrig-1 [ xref ], and supressors of cytokine signaling SOCS4/5 [ xref ]."
sparser
"c-Cbl can bind to the human EGFR in two ways, either directly to phosphorylated tyrosine-1045, or indirectly via binding to Grb2, which in turn binds to phosphorylated tyrosines -1068 and -1086 of the receptor ( xref )."
reach
"Interestingly, we also observed that binding of c-Cbl to EGFR was decreased in the presence of delta-catenin (XREF_FIG)."
CBL binds EGFR and GRB2. 10 / 31
| 29 2
sparser
"Binding of Grb2 and c-Cbl by EGFR is essential for infection."
sparser
"Residual ubiquitination was further consistent with the reported findings that Cbl can also interact indirectly with the EGFR through Grb2 ."
sparser
"However, it has no effect on the indirect binding of c-Cbl to EGFR via Grb2."
sparser
"On the other hand, the binding of Cbl to EGFR via Grb2 is important for receptor internalization [ xref ]."
sparser
"Here we use a simple modelling approach together with experiments to show that the establishment of the threshold requires both the multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR."
sparser
"Further, only indirect binding of Cbl to the EGFR through Grb2 is considered important for recruitment of the EGFR to clathrin-coated pits and thus essential for ligand-induced endocytosis of the EGF[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"In cell culture studies, the indirect binding of EGFR to Cbl through Grb2 is necessary for receptor internalization, whereas endosomal sorting requires direct binding to Cbl xref , xref ."
sparser
"In addition, Cbl can bind indirectly to the EGFR via Grb2 [ xref ]."
sparser
"Additionally, Cbl can also indirectly bind EGFR through the Grb2 adaptor protein at the Y1068 and Y1086 sites of the receptor xref ."
sparser
"Like c-Cbl, Grb2 bound EGFR more efficiently following EGF or BTC stimulation for 15 min compared with the other EGFR ligands ( xref )."
CBL binds EGF and EGFR. 8 / 8
| 8
sparser
"EGF was unable to induce ubiquitination of the serine-mutated EGFR, yet EGF-induced phosphorylation of the c-Cbl-binding site at tyrosine 1045, and c-Cbl-EGFR association, was unaffected."
sparser
"Co-immunoprecipitation studies demonstrated that Cbl became associated with the EGF receptor in an EGF-dependent manner."
sparser
"Further, c-Cbl associates only with EGF-EGFR homodimers, but not with EGF-EGFR/HER2 heterodimers, HER2, HER3, or HER4 ( Levkowitz et al., 1996 ; Muthuswamy et al., 1999 )."
sparser
"A further immuno-coprecipitation assay was conducted to examine the binding of EGFR and c-Cbl and EGF, but not anisomycin, induced the EGFR binding to c-Cbl (D)."
sparser
"Upon EGF binding, EGFR undergoes rapid phosphorylation, internalization and ubiquitination by the E3 ubiquitin ligase Cbl, which targets it for lysosomal degradation [ xref ]."
sparser
"In order to determine the role of c-CBL in differential degradation of EGFR mutants, we assessed EGFR and c-CBL binding, the effect of c-CBL knockdown on steady state levels of EGFR and c-CBL's effect on EGF and erlotinib-induced EGFR degradation (Figure xref )."
sparser
"The EGF-dependent rapid association of Cbl with the autophosphorylated EGF receptor observed in some [46, 49–54, 56, 57] , but not all [55] , studies is apparently mediated by the N-terminal region [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"EGF-induced c-Cbl-EGFR binding was partially inhibited, and receptor ubiquitination was abrogated in cells expressing Y1045F-EGFR."
SH3KBP1 binds CBL and EGFR. 7 / 7
| 7
sparser
"We have previously shown that CIN85 associates with Cbl and EGFRs following ligand stimulation, and remains in this complex during receptor trafficking to the lysosome [8,11] ."
sparser
"The coiled-coil domain, especially the basic amino acids in the domain, is the key regulatory element for the interactions of CIN85 with EGFR-Cbl as well as phosphatidic acid."
sparser
"CIN85 binds to activated EGFR through the E3 ligase Cbl to facilitate endocytosis and degradation ( xref ; xref ; xref ; xref )."
sparser
"As CIN85 with mutations in coiled-coil domain (CIN85-ΔCC, CIN85-16m or CIN85-A4m) dissociated from EGFR endosomes, their interaction with Vps proteins in cytoplasm prevented the Vps proteins to interact with EGFR-Cbl-CIN85 complex on endosomal membrane."
sparser
"The interaction of CIN85 with EGFR-Cbl complex and phosphatidic acid targeted the internalized proteins to membrane areas enriched with fusogenic lipid."
sparser
"The interaction of CIN85-SH3 with c-Cbl competes off the binding of functional CIN85 to EGFR-Cbl complex."
sparser
"The endogenous CIN85 can still be recruited by c-Cbl to form EGFR-Cbl-CIN85 complex, which then recruits endocytic proteins for receptor internalization."
CBL affects EGFR
2 95 10 | 11 236 141
2 95 10 | 11 192 139
biogrid
No evidence text available
reach
"The 16E5 effect on EGFR levels was similar to that seen by proteosomal inhibition, suggesting that interfering with the EGFR and c-Cbl interaction was an important contributor to E5 activation of EGFR."
sparser
"Therefore, we conclude that direct interaction between Cbl and EGFR may not be necessary for ligand-receptor endocytosis in vertebrate and invertebrate cells."
sparser
"Cdc42 is proposed to function in a positive feedback loop with the EGFR whereby epidermal growth factor (EGF) stimulates activation of Cdc42 and its interaction with specific target proteins: Cdc42, in turn, inhibits EGFR degradation by preventing binding of c-Cbl to EGFR."
sparser
"To test binding of Cbl proteins to EGFR, we prepared whole lysates from EGF-stimulated A-431 cells and incubated them for 1 hr at 4°C with immobilized GST–Cbl proteins."
sparser
"Other proteins that are capable of binding to Cbl and/or EGFR and implicated in the regulation of EGFR internalization and degradation are: Alix [ xref ], c-Abl tyrosine kinase [ xref ], Sts1/TULA2 [ xref ], Lrig-1 [ xref ], and supressors of cytokine signaling SOCS4/5 [ xref ]."
sparser
"c-Cbl can bind to the human EGFR in two ways, either directly to phosphorylated tyrosine-1045, or indirectly via binding to Grb2, which in turn binds to phosphorylated tyrosines -1068 and -1086 of the receptor ( xref )."
reach
"Interestingly, we also observed that binding of c-Cbl to EGFR was decreased in the presence of delta-catenin (XREF_FIG)."
CBL binds EGFR and GRB2. 10 / 31
| 29 2
sparser
"Binding of Grb2 and c-Cbl by EGFR is essential for infection."
sparser
"Residual ubiquitination was further consistent with the reported findings that Cbl can also interact indirectly with the EGFR through Grb2 ."
sparser
"However, it has no effect on the indirect binding of c-Cbl to EGFR via Grb2."
sparser
"On the other hand, the binding of Cbl to EGFR via Grb2 is important for receptor internalization [ xref ]."
sparser
"Here we use a simple modelling approach together with experiments to show that the establishment of the threshold requires both the multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR."
sparser
"Further, only indirect binding of Cbl to the EGFR through Grb2 is considered important for recruitment of the EGFR to clathrin-coated pits and thus essential for ligand-induced endocytosis of the EGF[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"In cell culture studies, the indirect binding of EGFR to Cbl through Grb2 is necessary for receptor internalization, whereas endosomal sorting requires direct binding to Cbl xref , xref ."
sparser
"In addition, Cbl can bind indirectly to the EGFR via Grb2 [ xref ]."
sparser
"Additionally, Cbl can also indirectly bind EGFR through the Grb2 adaptor protein at the Y1068 and Y1086 sites of the receptor xref ."
sparser
"Like c-Cbl, Grb2 bound EGFR more efficiently following EGF or BTC stimulation for 15 min compared with the other EGFR ligands ( xref )."
CBL binds EGF and EGFR. 8 / 8
| 8
sparser
"EGF was unable to induce ubiquitination of the serine-mutated EGFR, yet EGF-induced phosphorylation of the c-Cbl-binding site at tyrosine 1045, and c-Cbl-EGFR association, was unaffected."
sparser
"Co-immunoprecipitation studies demonstrated that Cbl became associated with the EGF receptor in an EGF-dependent manner."
sparser
"Further, c-Cbl associates only with EGF-EGFR homodimers, but not with EGF-EGFR/HER2 heterodimers, HER2, HER3, or HER4 ( Levkowitz et al., 1996 ; Muthuswamy et al., 1999 )."
sparser
"A further immuno-coprecipitation assay was conducted to examine the binding of EGFR and c-Cbl and EGF, but not anisomycin, induced the EGFR binding to c-Cbl (D)."
sparser
"Upon EGF binding, EGFR undergoes rapid phosphorylation, internalization and ubiquitination by the E3 ubiquitin ligase Cbl, which targets it for lysosomal degradation [ xref ]."
sparser
"In order to determine the role of c-CBL in differential degradation of EGFR mutants, we assessed EGFR and c-CBL binding, the effect of c-CBL knockdown on steady state levels of EGFR and c-CBL's effect on EGF and erlotinib-induced EGFR degradation (Figure xref )."
sparser
"The EGF-dependent rapid association of Cbl with the autophosphorylated EGF receptor observed in some [46, 49–54, 56, 57] , but not all [55] , studies is apparently mediated by the N-terminal region [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"EGF-induced c-Cbl-EGFR binding was partially inhibited, and receptor ubiquitination was abrogated in cells expressing Y1045F-EGFR."
SH3KBP1 binds CBL and EGFR. 7 / 7
| 7
sparser
"We have previously shown that CIN85 associates with Cbl and EGFRs following ligand stimulation, and remains in this complex during receptor trafficking to the lysosome [8,11] ."
sparser
"The coiled-coil domain, especially the basic amino acids in the domain, is the key regulatory element for the interactions of CIN85 with EGFR-Cbl as well as phosphatidic acid."
sparser
"CIN85 binds to activated EGFR through the E3 ligase Cbl to facilitate endocytosis and degradation ( xref ; xref ; xref ; xref )."
sparser
"As CIN85 with mutations in coiled-coil domain (CIN85-ΔCC, CIN85-16m or CIN85-A4m) dissociated from EGFR endosomes, their interaction with Vps proteins in cytoplasm prevented the Vps proteins to interact with EGFR-Cbl-CIN85 complex on endosomal membrane."
sparser
"The interaction of CIN85 with EGFR-Cbl complex and phosphatidic acid targeted the internalized proteins to membrane areas enriched with fusogenic lipid."
sparser
"The interaction of CIN85-SH3 with c-Cbl competes off the binding of functional CIN85 to EGFR-Cbl complex."
sparser
"The endogenous CIN85 can still be recruited by c-Cbl to form EGFR-Cbl-CIN85 complex, which then recruits endocytic proteins for receptor internalization."
GRB2 affects EGFR
5 2 51 10 | 5 288 129
3 2 51 10 | 5 199 126
sparser
"Proline-rich motifs in the N-terminus of RhoU mediate its interaction with GRB2 and the EGFR."
sparser
"For the TIR-FRET screening of larger cell collectives, we performed three separate steps: (1) setting up of a membrane associated test system for probing the interaction between the epidermal growth factor receptor (EGFR) and the growth factor receptor-bound protein 2; (2) use of the Epac-SH188 sensor for quantitative evaluation under the microscope; and (3) application of a TIR fluorescence reader to probe the interaction of GFP with Nile Red."
reach
"Receptor clusters of 100 increase the efficiency of Grb2 rebinding to a second EGFR by 6 fold, compared to randomly distributed receptors at this normal expression level."
sparser
"For example, the GRB2 adaptor protein binds activated EGFR at phosphorylated Tyr1068 xref , and phosphorylated Tyr1173 provides a docking site for the Shc scaffold protein, which is involved in mitogen-activated protein kinase (MAPK) signaling activation xref ."
reach
"It has been shown that EGF activated EGFR interacts with Grb2 at the plasma membrane and in endosomes XREF_BIBR, XREF_BIBR."
biogrid
No evidence text available
reach
"For example, activated EGFR binds to Shc and Grb2, which recruits Sos to the plasma membrane to activate Ras."
sparser
"We also demonstrated the ability of the peptides to block the binding of the GRB2 SH2 domain to EGFR in a mammalian cell-based binding assay."
sparser
"Additionally, the PLA to detect EGFR-GRB2 interaction was evaluated as a prognostic marker in two cohorts of patients with lung adenocarcinoma."
CBL binds EGFR and GRB2. 10 / 31
| 29 2
sparser
"Binding of Grb2 and c-Cbl by EGFR is essential for infection."
sparser
"Residual ubiquitination was further consistent with the reported findings that Cbl can also interact indirectly with the EGFR through Grb2 ."
sparser
"However, it has no effect on the indirect binding of c-Cbl to EGFR via Grb2."
sparser
"On the other hand, the binding of Cbl to EGFR via Grb2 is important for receptor internalization [ xref ]."
sparser
"Here we use a simple modelling approach together with experiments to show that the establishment of the threshold requires both the multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR."
sparser
"Further, only indirect binding of Cbl to the EGFR through Grb2 is considered important for recruitment of the EGFR to clathrin-coated pits and thus essential for ligand-induced endocytosis of the EGF[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"In cell culture studies, the indirect binding of EGFR to Cbl through Grb2 is necessary for receptor internalization, whereas endosomal sorting requires direct binding to Cbl xref , xref ."
sparser
"In addition, Cbl can bind indirectly to the EGFR via Grb2 [ xref ]."
sparser
"Additionally, Cbl can also indirectly bind EGFR through the Grb2 adaptor protein at the Y1068 and Y1086 sites of the receptor xref ."
sparser
"Like c-Cbl, Grb2 bound EGFR more efficiently following EGF or BTC stimulation for 15 min compared with the other EGFR ligands ( xref )."
SHC binds EGFR and GRB2. 10 / 23
| 23
sparser
"An earlier study has shown that Grb2 can interact with EGFR indirectly through Shc ( xref ; xref ), enabling the SH2 domain of Grb2 to interact with other proteins."
sparser
"Notably, activated EGFR interacts with Shc and Grb2 not only at the plasma membrane but also in the endosomal compartment, where EGF induces augmented recruitment of Shc and Grb2."
sparser
"We first describe our strategy to inhibit Grb2/Sos interaction at the level of its SH3 domains and then report the results obtained in blocking Grb2 SH2 domain interaction with EGF-R or Shc."
sparser
"Sem-5 is homologous to the mammalian protein Grb2, which binds the autophosphorylated EGF receptor and other phosphotyrosine-containing proteins such as Shc through its SH2 domain."
sparser
"The phosphorylation of these receptors, such as EGFR, also induces the tyrosine phosphorylation of the adapter protein SHC and the association of SHC with Grb2."
sparser
"EGFR binding and phosphorylation of Shc and Grb2 initiate this pathway, either by association directly with Grb2, or with a Shc-Grb2 complex (Rozakis-Adcock et al., 1992; Batzer et al., 1994)."
sparser
"The Src kinase, Yes, is activated by CCK and mediates EGFR Shc-Grb2 interactions ( xref )."
sparser
"The concentrations of EGF for which PI 3-kinase inhibitors block Ras activation induce formation of Shc-Grb2 complexes but not detectable EGF receptor phosphorylation and do not activate PI 3-kinase."
sparser
"Surprisingly, EGF and TGF-alpha induced full activation of MAPK in duration and intensity and stimulated association of the EGFR with Shc and Grb2."
sparser
"By contrast, Shc and Grb2 were inducibly associated with the EGFR in response to EGF stimulation of glioma cells."
SOS binds EGFR and GRB2. 10 / 17
| 17
sparser
"Upon EGFstimulation of the cell, binding of Sos to the EGF receptor-Grb2 complex brings a significant portion of Sos to the membrane (Figure 5)."
sparser
"EGF treatment of cells promotes the formation of a complex of EGF receptor, Grb2, and Sos."
sparser
"The measurable catalytic exchange activity of Sos in immunocomplex is unaltered by the association of Sos with EGF receptor and Grb2, either when the association occurs in EGF- stimulated cells or by [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways."
sparser
"As expected, mutation of the Grb2 binding site significantly reduced the interaction of Grb2 and SOS with EGFR ( xref )."
sparser
"We only considered this effect for the assembly of the EGFR-Grb2-Sos complex, but other components of the EGRF signaling network may also decrease their mobility upon activation."
sparser
"Zhang used this system to demonstrate the Grb2-mediated interaction of the cytoplasmic domain of the epidermal growth factor receptor with the Sos protein."
sparser
"Following EGFR activation, Grb2 and Sos (adaptor proteins) bind EGFR directly at Y1092 and Y1110 or through Shc (which binds at EGFR Y1172 and Y1197) [ xref ]."
sparser
"If the stimulation of exchange activity measured in this permeabilized cell system was due to the formation of EGF receptor-Grb2-Sos complexes, then it may be possible to inhibit it by the use of t[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"In response to epidermal growth factor (EGF), the activated EGF receptor binds to a complex containing the signaling protein GRB2 and the Ras guanine nucleotide-releasing factor Sos, leading to activation of the Ras signaling pathway."
EGF binds EGFR and GRB2. 10 / 16
2 | 14
sparser
"Upon EGF stimulation, Grb2 binds phosphorylated EGFR and activates the signaling pathway xref , xref ."
sparser
"Together these data indicate that AG-1478 inhibits both constitutive as well as EGF-induced EGFR-Grb2 interaction."
sparser
"Preclinical studies revealed cetuximab could decrease cell proliferation and phosphorylation of EGFR, and blocked the binding of the adaptor protein Grb2 to EGFR upon activation by EGF [ xref ]."
sparser
"Interestingly, in spite of the free phosphonate group with its negative charges, CGP78850 inhibited association of Grb2 with EGFR in intact serum-starved MDA-MB-468 triple-negative breast cancer cells stimulated with EGF in vitro ."
sparser
"Our results support the concept that EGFR interacts with Grb2 in both constitutive and EGF-dependent manners and this interaction is independent of HER3 co-expression."
sparser
"1) Association of Grb2 to EGFR in BxPC-3 induced by EGF in the presence of Erbitux indicates an alternate pathway of Ras-MAPK activation, which may be related with the tumor resistance to treatment; 2) transactivation of EGFR downstream Ras-MAPK pathway by FGF contributes the resistance to treatment; and 3) downregulation of EGFR may increase the response to therapy."
sparser
"Compound inhibited epidermal growth factor (EGF)-induced protein–protein interactions between EGFR (EGF receptor) and Grb2 in MDA-MB-468 cells and inhibited Ras activation in the same cell line."
sparser
"We identified that As 2 O 3 activates EGFR and promotes phosphorylation of p66 ShcA and its interaction with the Grb2 adaptor protein with slower kinetics compared to EGF-mediated EGFR activation."
sparser
"Because Ras activation by EGF involves EGF-stimulated association of EGF-R with Grb2, the EGF-R was immunoprecipitated and a Western blot was probed for Grb2."
sparser
"Pre-clinical studies showed cetuximab decreased cell proliferation and phosphorylation of EGFR, and blocked the binding of the adaptor protein Grb2 to EGFR upon activation by EGF [ xref ]."
LRRK1 binds EGFR and GRB2. 7 / 7
| 6 1
sparser
"We recently showed that LRRK1 forms a complex with activated EGFR through a mutual interaction with Grb2 ( xref )."
sparser
"Our results demonstrate that LRRK1 forms a complex with EGFR via Grb2 and associates with STAM and Hrs in response to ligand stimulation."
sparser
"LRRK1 forms a complex with activated EGFR via Grb2."
reach
"Interestingly, LRRK1 has been proposed to regulate endocytosis of EGFR via formation of a LRRK1, Grb2, and EGFR complex, while LRRK2 did not appear to form such a complex in this study suggesting that the two have functionally diverged."
sparser
"Interestingly, LRRK1 has been proposed to regulate endocytosis of EGFR via formation of a LRRK1-Grb2-EGFR complex ( xref ), while LRRK2 did not appear to form such a complex in this study suggesting that the two have functionally diverged."
sparser
"In this paper, we demonstrate that leucine-rich repeat kinase LRRK1, which contains a MAPKKK-like kinase domain, forms a complex with activated EGFR through an interaction with Grb2."
sparser
"We previously reported that LRRK1 forms a complex with activated EGFR through an interaction with Grb2 ( xref )."
EGFR affects GRB2
5 2 51 10 | 5 288 129
3 2 51 10 | 5 199 126
sparser
"Proline-rich motifs in the N-terminus of RhoU mediate its interaction with GRB2 and the EGFR."
sparser
"For the TIR-FRET screening of larger cell collectives, we performed three separate steps: (1) setting up of a membrane associated test system for probing the interaction between the epidermal growth factor receptor (EGFR) and the growth factor receptor-bound protein 2; (2) use of the Epac-SH188 sensor for quantitative evaluation under the microscope; and (3) application of a TIR fluorescence reader to probe the interaction of GFP with Nile Red."
reach
"Receptor clusters of 100 increase the efficiency of Grb2 rebinding to a second EGFR by 6 fold, compared to randomly distributed receptors at this normal expression level."
sparser
"For example, the GRB2 adaptor protein binds activated EGFR at phosphorylated Tyr1068 xref , and phosphorylated Tyr1173 provides a docking site for the Shc scaffold protein, which is involved in mitogen-activated protein kinase (MAPK) signaling activation xref ."