IndraLab

Statements


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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."
reach
"For example, activated EGFR binds to Shc and Grb2, which recruits Sos to the plasma membrane to activate Ras."
sparser
"Additionally, the PLA to detect EGFR-GRB2 interaction was evaluated as a prognostic marker in two cohorts of patients with lung adenocarcinoma."
reach
"The underlying mechanism seems to involve recruitment of a Grb2 c and Cbl complex to Grb2 specific docking sites of EGFR, and concurrent acceleration of receptor ubiquitylation and desensitization."
reach
"The interaction between Grb2 and activated EGF receptor is likely to be mediated by the SH2 domain of Grb2 binding to one, or more, of the tyrosine autophosphorylation sites in the carboxy-terminal ta[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"Therefore, our data with AG-1478 clearly demonstrate that (i) EGFR homomers are constitutively interacting with Grb2 in HEK293FT cells, which may be due to some constitutive activity of the receptor, at least with regard to the Grb2 pathway in this cell line, (ii) EGF- as well as HRG-induced Grb2 recruitment strictly depends on receptor activation (constitutive or ligand-induced), and (iii) the recruitment of Grb2 to HER3 is observed only when HER3 is engaged in a heteromer complex with another receptor subtype such as EGFR."
sparser
"Grb2, which is constitutively associated via its SH3 domain with Grb2-associated binder 1 (Gab1), binds to the EGFR."
sparser
"The highest photo-cross-linking yield for Grb2-D104mPyTK was observed when cells were stimulated with EGF for 15 min (Figure S11B in), indicating that the Grb2EGFR interaction is transient and dynamic, resembling some other known EGF-dependent protein–protein interactions. xref "
reach
"Interestingly, the relatively rapid kinetics of EGFR-GRB2 binding, 17 which may not prevail for all EGFR adaptors, produces EGFR and GRB2 complex sensitivity results that are indistinguishable from those for phosphorylated receptor."
sparser
"The relative lack of importance of the +2 position in determining EGFR efficiency allows specification of Grb2 binding independent of EGFR phosphorylation."
biogrid
No evidence text available
sparser
"Following activation of the EGFR kinase and autophosphorylation, the SH2 domain of Grb2 can bind to the EGFR."
reach
"From these studies, we concluded that Grb2 binds directly to the EGFR at Y-1068, to a lesser extent at Y-1086, and indirectly at Y-1173."
reach
"Several studies have suggested that the recruitment of CIN85 and Grb2 to EGF-R via Cbl regulates receptor internalization and degradation [17-20]."
biogrid
No evidence text available
sparser
"We provide proof of concept for the detection of protein proximity pairs (β-Catenin:E-Cadherin and EGFR:GRB2), and confirm assay specificity through technical controls involving reagent omission experiments, and biologically by treatment with small molecule kinase inhibitors that interrupt kinase:adaptor complexes."
trips
"Competition experiments with synthetic phosphopeptides corresponding to known autophosphorylation sites on the EGFR demonstrated that phosphopeptides containing Y-1068, and to a lesser extent Y-1086, were able to inhibit the binding of Grb2 to the EGFR, while a Y-1173 peptide did not."
sparser
"It has been shown that EGF-activated EGFR interacts with Grb2 at plasma membrane and in endosomes ( xref ; xref )."
biogrid
No evidence text available
sparser
"In cells expressing the EGF receptor, growth hormone was able to promote GRB-2 association with the EGF receptor, MAP kinase activation, and c- fos induction."
reach
"The EGF receptor can interact with Grb2 and the associated SOS protein stimulates ras."
sparser
"The latter possibility is supported by the observation that Grb2, which binds directly to phosphorylated Y1068 and Y1086 in activated EGFR, interacts with c-Cbl proline-rich domains via its SH3 domain and recruits Cbl to EGFR."
sparser
"Sorkin and co-workers previously established that FRET can be used to detect interactions between EGFR and Grb2, but no estimates of cluster sizes were made in that study. xref "
reach
"The functional consequence of Grb2 binding to the activated EGF receptor appears to be linked to the EGF- dependent accumulation of active (GTP bound) Ras."
trips
"From these studies, we concluded that Grb2 binds directly to the EGFR at Y-1068, to a lesser extent at Y-1086, and indirectly at Y-1173."
sparser
"As Grb2-EGFR interaction depends on phosphorylation of the EGFR, this demonstrates that the EGFR kinase remains active until translocation to inner vesicles of MVBs."
sparser
"For example, phosphorylation at Tyr-920 controls PI3K/Akt signaling through regulation of interactions of EGFR with p85, while phosphorylation at Tyr-1068 stimulates binding of EGFR with Grb2, which can trigger Ras/mitogen-activated protein (MAPK) signaling xref ."
reach
"To determine the necessity of the RhoU SH3 binding sites in coupling to the GRB2 and EGFR complex in vivo, we coimmunoprecipitated endogenous EGFR and GRB2 with Flag-RhoU."
sparser
"It has been shown that EGF-activated EGFR interacts with Grb2 at the plasma membrane and in endosomes xref , xref ."
biogrid
No evidence text available
sparser
"We evaluated whether desensitization of EGF-induced STAT3 phosphorylation could be associated with GRB2 up-regulation and/or increased association of Grb2 to the EGFR in the transgenic mice overexpressing GH, but no significant differences in GRB2 protein content or GRB2 association to EGFR between normal and transgenic mice were found ( xref )."
sparser
"The EGFR-binding adaptor, Grb2, binds to the phosphotyrosine residues of the activated receptor ( xref ) and to the guanine nucleotide exchange factor, SOS, through two SH3 domains of GRB2."
sparser
"In contrast to the activated EGF receptor, which binds the Grb2-Sosl complex directly, activation of insulin receptors leads to recruitment of Grb2-Sosl to two tyrosine-phosphoryl- ated proteins,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"In another example from the same figure, SOS is shown catalyzing guanine nucleotide exchange in Ras; Ras is shown binding to plasma membrane, and SOS can be recruited to the plasma membrane via its binding through Grb2 to the ErbBs (or more indirectly via Shc)."
reach
"An earlier study has shown that Grb2 can interact with EGFR indirectly through Shc, enabling the SH2 domain of Grb2 to interact with other proteins."
biogrid
No evidence text available
sparser
"Significantly, in agreement with our new experimental observations, the model predicts that Grb2 associates predominantly with EGFR tetramers."
sparser
"We incorporated mTmdZLys in place of lysine at position 109 in the SH2 domain of GRB2 ( xref ), and analysed the formation of the complex between this photo-cross-linkable GRB2 and the endogenous EGFR."
sparser
"This reduced EGFR kinase-dependence of the peroxide-induced R4 response was correlated to a significant reduction in the degree of peroxide-induced EGFR tyrosine phosphorylation ( xref ), attenuated peroxide-induced association of EGFR with Grb2 ( xref ) and a strong redistribution of EGFR away from the plasma membrane to the cytosol ( xref )."
reach
"Most importantly, alpha-LA disrupts the interaction of EGFR and Grb2, which prevents the activation of EGFR signaling and the MAPK and ERK pathway."
biogrid
No evidence text available
sparser
"Both CME and several NCE pathways are involved in EGFR internalization. [ xref ] The ubiquitination of EGFR is necessary for all internalization pathways, and the ubiquitin ligase responsible for EGFR ubiquitination is Cbl, a ring‐finger domain E3 ubiquitin ligase. [ xref ] Cbl can directly bind to EGFR, or indirectly bind to EGFR via the adaptor protein Grb2. [ xref , xref ] The EGFRGrb2‐Cbl complex is necessary for NCE, with previous studies showing that EGFR mutants lacking Grb2 binding sites are completely defective for NCE. [ xref , xref ] Our results indicated that SGCE knockdown caused induction of EGFR internalization, and increased the interaction between EGFR and c‐Cbl but not that between EGFR and Grb2."
reach
"Functional interaction of the EGFR with Grb2 and Shc1."
reach
"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."
reach
"Evidences have shown that GRB2 forms a complex with activated EGFR and the RAS specific guanine nucleotide exchange factor SOS1, thereby mediating the growth factor induced activation of RAS XREF_BIBR, XREF_BIBR."
biogrid
No evidence text available
biogrid
No evidence text available
sparser
"The EGFR-Grb2 interaction has been previously observed in the same compartments with a three-channel FRET imaging using the EGFR-EYFP and Grb2-ECFP fusion proteins ( xref )."
sparser
"The N-terminus of LRRK1 interacts with Grb2, an adaptor protein for EGFR, and LRRK1 forms a complex with EGFR via Grb2 in response to EGF stimulation."
sparser
"Considering that on average 74% of EGFRs make up the Grb2-bound population and 36% the unbound population, the normalized density for 100% Grb2-bound EGFR clusters would be 16 clusters/μm 2 and 100% Grb2-free EGFR clusters would be 63 clusters/μm 2 ."
sparser
"Instead, Gab1 likely becomes enriched within clathrin structures as a result of interactions with EGFR or Grb2 ( xref )."
reach
"We could not detect an increase in binding between EGFR and GRB2, ruling out a possible contribution of increased P-EGFR to P-ERK in this model (XREF_SUPPLEMENTARY)."
sparser
"It was recently shown that selective measurement of Grb2-EGFR interaction could prognostically predict therapeutic response, moreso than abundance or phosphorylation of EGFR ( xref )."
sparser
"In all of the cell types tested, Grb2 was associated with EGFR when cells were treated with EGF but was only present at lower levels in response to injury or 25-μmol/L UTP."
sparser
"GRB2 is required for survival of cells with mutant EGFR [ xref ] and the interaction between EGFR and GRB2 is abrogated by erlotinib, resulting in loss of downstream ERK signaling [ xref , xref ]."
reach
"Next, we studied the interaction between endogenous EGFR and fluorescent Grb2."
sparser
"The adaptor protein Grb2 (growth factor receptor-binding protein 2) binds to EGFR, which leads to activation of Ras-MAPK (mitogen-activated protein kinase) cascade."
sparser
"The biology behind the positive feedback loop in our example model is as follows [ xref ]: in response to growth factor stimulation, Gab1 is recruited to the plasma membrane through binding to the ErbB1-Grb2 complex."
biogrid
No evidence text available
biogrid
No evidence text available
sparser
"Most importantly, α-LA disrupts the interaction of EGFR and Grb2, which prevents the activation of EGFR signaling and the MAPK/ERK pathway."
sparser
"We developed a PLA to measure the interaction between EGFR and GRB2."
sparser
"Alternatively, blocking palmitoylation increased the association of EGFR with the MAPK adaptor Grb2 and decreased that with p85."
reach
"The EGF receptor binds Grb2 directly, and its Grb2 binding sites are also required for recruitment of Gab1 (Okutani et al. 1994; Rodrigues et al. 2000); thus, the EGF receptor may recruit Gab1 via Grb2-Gab1 complexes."
sparser
"After EGF stimulation, the Grb2 SH2 domain binds to the EGF receptor directly or indirectly through proteins such as Shc, FAK, Syp, and IRS-1, by recognizing phosphotyrosine (pTyr)-containing sequences."
reach
"When activated epidermal growth factor receptor (EGFR) and pBpA containing Grb2 are co-expressed and treated with UV light, a larger molecular weight band is detected suggesting the binding of EGFR to Grb2."
sparser
"Our adaptive signaling model is supported by recent work using phosphoproteomic approaches, which demonstrated that GRB2 was bound to EGFR in unperturbed ALK+ lung cancer cells and that EGFR phosphorylation increased in response to crizotinib treatment ( xref )."
reach
"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."
reach
"This result suggests that in the context of a simple monomer and N-mer equilibrium the cluster size of the Grb2 bound EGFR is approximately 4."
reach
"Grb2 binds activated EGFR at phosphotyrosines 1068/1086, and induces ERK1/2 signaling via Ras and Raf, rather than the MAP kinase pathway."
sparser
"With this approach, we confirm the previously characterized interaction between Grb2 and the EGF receptor, and we identify novel partners of the IGF-1 receptor and of the JAK proteins."
sparser
"Phosphorylated Y1068 on EGFR binds to the adapter molecule Grb2."
reach
"16 Given that receptor-adaptor association is required for downstream signaling, however, computing the IC 50 for EGFR and GRB2 complex formation may provide additional insight."
sparser
"Next, we studied the interaction between endogenous EGFR and fluorescent Grb2."
sparser
"Conversely, ShcC failed to bind EGFR or Grb2 and undergo phosphorylation ( xref ), confirming that it is not a physiological substrate of the EGFR, as previously shown ( xref )."
biogrid
No evidence text available
sparser
"Therefore, it is tempting to speculate that hPIV3-C interaction with GRB2 and EGFR pathway participates in such deregulation of airway epithelium homeostasis to promote hPIV3 replication and spreading."
sparser
"To provide additional evidence for the switchable pcFRET, we next measured the EGFR-EYFP and Grb2-rsTagRFP interaction in live cells, using the FLIM technique."
trips
"Live-cell fluorescence imaging reveals high stoichiometry of Grb2 binding to the EGF receptor sustained during endocytosis."
hprd
No evidence text available
reach
"Complexes that contain SHC have been reported to be better at activating RAS than those without SHC (i.e., direct binding of GRB2 to EGFR) [XREF_BIBR]."
reach
"Furthermore, Western blotting of Grb2 immunoprecipitates with anti-EGFR showed that Grb2 was bound to the EGFR in response to EGF."
biogrid
No evidence text available
signor
"Erbb1 recruites grb2 through sh2 domain;from these studies, we concluded that grb2 binds directly to the egfr at y-1068, to a lesser extent at y-1086, and indirectly at y-1173. Egfr has six binding sites for the adapter protein grb2, and erbb4 has five, each with different binding strength several tyrosine-based motifs recruit a number of signal transducers to the phosphorylated form of erbb1 such as the adaptor proteins growth-factor-receptor bound-2 (grb2) and src-homology-2-containing (shc)."
reach
"The adaptor protein Grb2 (growth factor receptor binding protein 2) binds to EGFR, which leads to activation of Ras-MAPK (mitogen activated protein kinase) cascade."
sparser
"Using pcFRET, EGFR-Grb2 interactions could be detected in the same cells at different time points, both before and after EGF stimulation."
reach
"The tyrosine phosphorylated tail of the EGF receptor binds Ras-GAP, PLCy, Grb2 and Shc ([8,111; AG Batzer, D Rotin, JM Ure, EY Skolnik, J Schlessinger, unpublished data)."
sparser
"The hypothesis proposed was that Grb2 repeatedly interacts with EGFR for short times, accelerating substrate transitions in a way that increases the time constant of association."
sparser
"The use of the PLA assay to detect EGFR binding to GRB2 as a surrogate for activation has been previously described [17] but never quantitatively measured."
sparser
"Sensitivity of EGFR-Grb2 interaction."
reach
"Upon EGFstimulation of the cell, binding of Sos to the EGF receptor and Grb2 complex brings a significant portion of Sos to the membrane."
sparser
"We did not observe enhanced interaction between EGFR and GRB2 (Figure S6H, Supporting Information)."
sparser
"To test whether nicotine-activated EGFR was able to bind to Grb2, MCF10A cells were treated with nicotine or EGFR and immunoprecipitation was then performed (Figure xref )."
reach
"The model represents ErbB1 synthesis and degradation; EGF ligand binding to ErbB1; receptor dimerization and activation; activation of the signaling pathways associated with the binary interactions between ErbB1 + Shc, Shc + Grb2, ErbB1 + Shc-Grb2, ErbB1 + Grb2, and Grb2 + Sos; deactivation of ErbB1 following PTP + ErbB1 interactions; and dissociation of active Shc from ErbB1."
reach
"In this pathway, activated EGFR binds GRB2 associated binding protein 1 together with growth factor receptor bound protein 2 to recruit PI3K."
biogrid
No evidence text available
sparser
"An epidermal growth factor receptor mutant lacking all known autophosphorylation sites is unable to bind to the GRB2 molecule, yet can still induce SHC phosphorylation and RAS activation in fibrobl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
reach
"We found EGFR bound to GRB2, suggesting how EGFR signaling can control this network and drive resistance to ALK TKI by facilitating EGFR : GRB2 signaling complexes."
sparser
"However, the interaction of EGFR and Grb2 can be clearly stimulated; the addition of EGF resulted in a prominent increase of the Grb2-YFP fluorescence within EGFR-enriched μ-patterns."
reach
"A recent report showed that GRB2 interacted directly with Ras homolog family member U (RhoU) and with activated EGFR, leading to augmented JNK1 pathway activity and cell migration XREF_BIBR."
reach
"An EGFR derived phosphopeptide bound Grb2 with a KD of 0.7 microM, whereas the Shc derived phosphopeptide bound Grb2 with a KD of 0.2 microM."
sparser
"It is therefore likely that the interaction of Grb2 with the EGF receptor serves to relocalize a con- stitutively active Sosl from the cytosol to the plasma membrane, increasing the local concent[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
biogrid
No evidence text available
reach
"Our immunoprecipitation results indicate that there are enhanced interactions between EGFR and Ras and EGFR and Grb2 after both 3- (XREF_FIG) and 14-days (XREF_FIG)."
sparser
"Following EGF stimulation, GRB2 directly binds to the cytoplasmic domain of the EGFR at phosphorylated residues Tyr1068 and Tyr1086 to initiate the activation of the Ras/MAPK pathway ( xref )."
sparser
"We continued our work by analyzing the relevance of CCPs for the binding of Grb2 to the EGFR."
sparser
"Moreover, blocking of the interaction between Grb2 and the phosphorylated EGF receptor with a phosphopeptide corresponding to the EGF receptor Grb2-binding site resulted in inhibition of EGF-induced p[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
biogrid
No evidence text available
reach
"The use of the PLA assay to detect EGFR binding to GRB2 as a surrogate for activation has been previously described [17] but never quantitatively measured."
reach
"The importance of the kinase domain of HER3 (not removed by the truncation) for EGFR dependent Grb2 interaction is in agreement with the recent structural study showing that although the HER3 kinase domain is not functional in terms of kinase activity, it can activate the EGFR kinase domain by formation of the asymmetric dimer XREF_BIBR."
reach
"In contrast to the activated EGF receptor, which binds the Grb2 and Sosl complex directly, activation of insulin receptors leads to recruitment of Grb2-Sosl to two tyrosine phosphoryl- ated proteins, [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
biogrid
No evidence text available
reach
"Interaction between activated EGFR and Grb2 at the endosomes upon EGF stimulation was proven by FRET microscopy [5]."
biogrid
No evidence text available
reach
"We did not observe enhanced interaction between EGFR and GRB2."
reach
"Grb2 binds to the activated EGFR and acts as an adaptor to recruit the E3 ubiquitin ligase Casitas B lineage lymphoma protein to start internalization."
sparser
"These values were determined in our EGFR (Epidermal Growth Factor Receptor) assay, which measures the potency of a compound to inhibit the binding of the phosphorylated intracellular domain of EGFR t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"It has been shown by a number of laboratories that the SH2 domain of Grb2 binds to the tyrosine phosphorylated EGF receptor [33,51,72,73] ."
sparser
"Alternatively, association of GRB2 to EGFR could be increased in the transgenic mice."
biogrid
No evidence text available
sparser
"As shown in Fig.  xref b, the dose- and time-dependent increases in Grb2 SH2 binding to EGFR were obvious both by far-Western (~180 KDa band on upper panel) and SH2-PLA (Ct value in lower panel)."
biogrid
No evidence text available
sparser
"In vitro interaction of cell-free synthesized EGFR with Grb2."
hprd
No evidence text available
sparser
"Accordingly, the estimated size of clusters containing Grb2-bound EGFR would be about 4.2 ± 1 receptors/cluster and the estimated size of clusters free of Grb2 would be about 1.1 ± 0.3 receptors/cluster."
reach
"EGFR is able to activate PI3K through a series of reactions : active EGFR binds adaptor protein Grb2, which recruits the docking protein Gab1, which contains pYXXM motifs to which SH2 domains on the regulatory subunit of PI3K (p85) bind, thereby bringing the catalytic subunit of PI3K (p110) in proximity to its membrane bound lipid substrates [XREF_BIBR]."
sparser
"This reduced EGFR kinase dependence of the peroxide-induced R4 response was correlated to a significant reduction in the degree of peroxide-induced EGFR tyrosine phosphorylation ( xref ), attenuated peroxide-induced association of EGFR with Grb2 (Figures xref and xref ), and a strong redistribution of EGFR away from the plasma membrane to the cytosol (Figures xref and xref )."
biogrid
No evidence text available
reach
"These interactions between EGFR and Grb2 were detected based on the colocalization of fluorescent spots."
hprd
No evidence text available
biogrid
No evidence text available
sparser
"Recent studies also found that PLA signals corresponding to EGFR-related interactions such as those between EGFR and GRB2 or between nonphosphorylated and phosphorylated forms of EGFR were higher in NSCLC cell lines positive for EGFR mutations than in those WT for EGFR [ xref – xref ]."
sparser
"Next, we found two components of the Egfr pathway, whose function consists of the adaptor molecule Grb2 binding to Egfr with the subsequent activation of the pathway."
reach
"The primary protein-receptor interactions included Grb2 binding to ErbB1 (ErbB1-Grb2) and Shc binding directly to ErbB1 (ErbB1-Shc)."
sparser
"Sorkin, A., McClure, M., Huang, F., Carter, R. (2000): Interaction of EGF receptor and grb2 in living cells visualized by fluorescence resonanceenergytransfer(FRET)microscopy."
sparser
"Previous studies have reported p66Shc's ability to bind epidermal growth factor receptor (EGFR) and Grb2 in the absence of receptor stimulation in various cell types [ xref , xref , xref , xref ]."
reach
"Earlier work has shown that the signaling activity of EGFR is potentiated in endosomes, as judged by a high stoichiometry of Grb2 binding to EGFR [XREF_BIBR]."
sparser
"Moreover, cell lines with increased EGFR:GRB2 PLA signal had increased abundance of Tyr 1068 phosphorylated EGFR ( xref ) and a robust interaction between EGFR and GRB2 as determined by coimmunoprecipitation ( xref )."
sparser
"Thus upon autophosphorylation of the EGFR cytoplasmic domain the SH2 domain adapter protein Grb2 binds to phosphotyrosine residues, particularly Y-1068 in the tail region ( xref )."
sparser
"On activation of certain RTKs such as EGFR and MET, Gab1 is recruited to the plasma membrane via interaction with EGFR-bound Grb2 or directly with MET, followed by the phosphorylation of a number of tyrosine residues on Gab1 ( xref )."
sparser
"Due to the optical diffraction limit of microscopy, the observed overlapping of fluorescent spots did not necessarily indicate direct interaction between EGFR and GRB2."
reach
"Considering that on average 74% of EGFRs make up the Grb2 bound population and 36% the unbound population, the normalized density for 100% Grb2 bound EGFR clusters would be 16 clusters and mum 2 and 100% Grb2-free EGFR clusters would be 63 clusters and mum 2."
biogrid
No evidence text available
sparser
"Phosphorylation of EGFR Y1068 leads to GRB2 binding to EGFR which can increase downstream signalling of MEK/MAPK pathway."
sparser
"The inducibility of the Grb2Sos interaction by EGF implies that binding of EGF receptor to the SH2 domain of Grb2 transmits a conformational change to its SH3 domains, increasing their affinity for SO[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"Unlike the tyrosine phosphorylation and Grb2 interaction with the EGFR, repeated peroxide exposure (at R4 response point) did not significantly affect Pyk2 Tyr-881 phosphorylation ( xref ) or the Grb2 content of the Pyk2 immunoprecipitates ( xref )."
reach
"We developed a PLA to detect EGFR and GRB2 complexes that could be quantified using the AQUA (R) method of automated quantitative immunofluorescence (QIF) 18, eliminating any subjective interpretation of the results and allowing the objective and reproducible measurement of the obtained signal."
reach
"Like c-Cbl, Grb2 bound EGFR more efficiently following EGF or BTC stimulation for 15 min compared with the other EGFR ligands (XREF_FIG)."
sparser
"These results suggest that the cytoplasmic domain of EGFR binds GRB2 in multiple conformations and that the conformation bias depends on the size of the EGFR cluster."
sparser
"The importance of the kinase domain of HER3 (not removed by the truncation) for EGFR-dependent Grb2 interaction is in agreement with the recent structural study showing that although the HER3 kinase domain is not functional in terms of kinase activity, it can activate the EGFR kinase domain by formation of the asymmetric dimer xref ."
sparser
"A rule-based model reported earlier xref was extended to include one new rule for Grb2 interaction with phosphorylated EGFR (pEGFR) (Figures xref and xref )."
hprd
No evidence text available
reach
"In contrast to Shc, Grb2 and Ash bound to EGF receptor but did not form a stable complex with the NGF receptor."
sparser
"When activated epidermal growth factor receptor (EGFR) and pBpA containing Grb2 are co-expressed and treated with UV light, a larger molecular weight band is detected suggesting the binding of EGFR to Grb2 ( xref )."
biogrid
No evidence text available
biogrid
No evidence text available
reach
"The EGFR interacts with adaptor proteins Grb2 and SOS, activating Ras and Raf, followed by phosphorylation of Mitogen activated protein kinase and ERK and extracellular signal regulated kinase (ERK)."
biogrid
No evidence text available
reach
"The reaction of association between active EGFR and Grb2 is represented using an open headed ' transport ' arrow and a circle headed ' catalysis ' arrow as a local rule adopted in this map ver."
sparser
"Ectopically expressed Mig6 or mutant Mig6 deficient for Grb2 binding (PP319/20AA) coimmunoprecipitated with EGFR and inhibited EGFR autophosphorylation, as shown by western analysis ( xref D)."
sparser
"The largest module consists of 32 ODEs and describes Grb2 binding to the EGF receptor as well as to phosphorylated Shc."
reach
"Indeed as found by several groups, Drk binds both to the activated Sevenless receptor and SOS, and Grb2 binds both to the activated EGF receptor and mammalian SOS (MmSOS) [28,65,125,133,170, 195,213]."
sparser
"These discoveries were extended to mammalian systems, where it was shown that the Grb2 SH2 domain could inducibly bind the tyrosine phosphorylated epidermal growth factor receptor (EGFR) while bound constitutively to son of sevenless (SOS), a guanine nucleotide exchange factor for Ras."
signor
"We determined interaction partners to all cytosolic tyrosine residues of the four members of the ErbB-receptor family in an unbiased fashion by quantitative proteomics using pull-down experiments with pairs of phosphorylated and nonphosphorylated synthetic peptides. Each receptor had characteristic preferences for interacting proteins and most interaction partners had multiple binding sites on each receptor. EGFR and ErbB4 had several docking sites for Grb2, while ErbB3 was characterized by six binding sites for PI3K."
sparser
"Grb2 binds to the EGF receptor directly through Tyr1068 and indirectly through the Shc binding site at Tyr1173."
sparser
"ShcD, however, was found to have a binding profile similar to that of ShcA and ShcB, in which EGF stimulates ShcD tyrosine phosphorylation and induces its interaction with EGFR and Grb2 ( xref )."
reach
"In this case, a multi-level logical description would be most appropriate : active Grb2 (i.e., Grb2 bound to ErbB1 homo- or heterodimers) activates Gab1 to level 1, whereas Grb2 AND PIP3 activate Gab1 to level 2."
reach
"Of interest, although dominant negative (DN) RhoU (T63N) interacted with EGFR and GRB2 complexes, deletion of the RhoU C-terminal extension abolished this interaction (XREF_FIG)."
sparser
"These results indicate that the binding of Grb2 to the phosphorylated Tyr-1068 of EGFR is crucial to the EGF-induced Ras/mitogen-activated protein kinase signaling pathway."
reach
"First, we investigated whether the three peptide candidates induced a physical interaction between EGFR and Grb2 or Gab1 and SHP2."
sparser
"However, this notion was challenged by the demonstration that the majority of active EGF receptors and associated signaling molecules localize to early endosomes shortly after ligand stimulation [ xref – xref ], and that active EGF receptor interacts with Grb2 [ xref ] and engages the major signaling pathways required for cell survival and mitogenesis after endocytosis [ xref , xref ]."
reach
"Again, a higher order complex could enable recruitment of Grb2 and Venus to a second untagged EGFR protomer rather than HER3 and Rluc8, which would be expected to result in a lower BRET signal as is indeed observed in XREF_FIG compared to 6b."
sparser
"Hence, in response to EGF- 274 receptor autophosphorylation, a pre- existing Grb2-Sosl complex binds to the EGF receptor, recruiting Sos to the plasma membrane where the Ras pro- tein is locat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
reach
"As Grb2 binding to the EGFR decreases, ligand induced EGFR intracellular signaling also decreases [93]."
bel
"In this study, we describe the specific interaction of PAK1 with the Grb2 adapter protein both in vitro and in vivo. We identify the site of this interaction as the second proline-rich SH3 binding domain of PAK1. Stimulation of the epidermal growth factor receptor (EGFR) in HaCaT cells enhances the level of EGFR-associated PAK1 and Grb2, although the PAK1-Grb2 association is itself independent of this stimulation. "
sparser
"14 This Tyr-X-Asn-X sequence is found in EGFR but not in the insulin receptor; therefore, GRB2 can bind directly to EGFR but not to the insulin receptor."
sparser
"Indeed, Grb2 associates with the EGFR either directly or indirectly (via Shc) through multiple major EGFR autophosphorylation sites [16,21] ."
reach
"We could not detect an increase in binding between EGFR and GRB2, ruling out a possible contribution of increased P-EGFR to P-ERK in this model."
sparser
"The t 50 for 1.6 nmol/l EGF and 1 µmol/l gefitinibis sensitive to perturbations in k dp,s and k dp,i , k p,L , k A,f and k A,r , k g,f and k g,r , k i , and parameters for GRB2-EGFR binding ( k G 2 ,f and k G 2 ,r ) ( xref )."
reach
"These results suggest that the cytoplasmic domain of EGFR binds GRB2 in multiple conformations and that the conformation bias depends on the size of the EGFR cluster."
sparser
"Cells were prestimulated with 20 nM of either EGF or HRG and therefore AG-1478 was seen to inhibit both the EGF-induced ( xref ) and constitutive ( xref ) interaction of EGFR homomers with Grb2, in a time-dependent manner."
sparser
"Since reduced p66 ShcA isoform is associated with increased survival [ xref ], we next assessed whether p66 ShcA could be involved in regulating As 2 O 3 -mediated increased interaction between EGFR with Grb2."
reach
"It appears that there are several redundant and possibly interdependent mechanisms, which involve : (a) EGFR binding to the clathrin endocytosis protein complex AP2, and to the phospho-tyrosine binding adaptor protein growth factor receptor bound protein 2 (Grb2); (b) ubiquitination of 15 lysines in the EGFR kinase domain by the E3 ubiquitin ligase Casitas B-lineage lymphoma (Cbl), and of 6 other lysines in the carboxy-terminus region; (c) acetylation of 3 of the latter lysines [XREF_BIBR]."
sparser
"In addition, RhoU is involved in EGFR-mediated signaling, leading to AP1 transcriptional activity and cell migration in pancreatic cancer cells, events that require its interaction with the Grb2EGFR complex."
sparser
"Following EGFR activation, Cbl is recruited through its constitutive binding partner Grb2 which directly binds to the EGFR tyrosine kinase binding domain via its SH2 domain ( xref )."
reach
"This basic interaction between Grb2 and EGFR appeared without any additional EGFR activation and may be caused by the stimulating nature of the antibody coated surface and/or the presence of growth factor containing serum."
reach
"However, mutation of C1025 has the strongest increas in the binding of EGFR with the adapter protein Grb2."
sparser
"The technique has also been used to investigate the binding of EGFR to the adaptor protein Grb2 [ xref ]."
sparser
"Thus, the binding of Grb2 to phosphorylated EGF receptor results in the recruitment of Sos to the plasma membrane and has been proposed as a model for activation of membrane-bound Ras [39] ."
biogrid
No evidence text available
sparser
"Grb2 binds to the activated EGFR and acts as an adaptor to recruit the E3 ubiquitin ligase Casitas B lineage lymphoma protein to start internalization."
sparser
"Since the activated sevenless is phosphorylated on tyrosine residues, we presume that the interaction between drk and sevenless is mediated by the SH2 domain of drk binding to tyrosine-phosphorylated [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"Subsequently, lipocortin-1 competitively inhibited Grb2 binding to EGFR, thereby blocking the recruitment of critical signaling molecules necessary for EGF actions [ xref ]."
sparser
"Following EGFR activation, the MAPK signaling pathway is triggered by the growth factor receptor-bound protein 2 (Grb2) binding directly to EGFR via Y1068 and Y1086 or indirectly by SHC binding Y1173 and Y1143 ( xref )."
sparser
"ACK1 is shown to bind EGFR in a Grb2-dependent manner and aids EGFR downregulation with its functional ubiquitin association domain (UBA) ( Grovdal et al., 2008; Kato-Stankiewicz et al., 2001; Shen et[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
reach
"A plausible explanation for cooperativity is that when Cbl and Grb2 are simultaneously bound to EGFR (via pY1045 and pY1068 and pY1086, respectively), they are in a state of enforced proximity, which increases the likelihood of the three species (EGFR, Cbl and Grb2) of binding to each other XREF_BIBR."
sparser
"Mutation of palmitoylated cysteine residues increases EGFR interaction with Grb2."
sparser
"The proposed mechanism involved in such desensitization implies GRB2 binding to the EGFR, inhibiting the interaction between STAT3 and EGFR by competitive binding to the same region of the receptor ( xref )."
reach
"To demonstrate the utility of rsTagRFP as a switchable pcFRET acceptor, we next studied the interaction between EGFR and Grb2 that is induced upon stimulation with epidermal growth factor (EGF) in mammalian cells."
hprd
No evidence text available
sparser
"Work done by Gay et al. using CGP78850 (compound 41 , Fig.  xref ), a selective Grb2 SH2 domain-binding inhibitor having a mixed phosphoramidite/phenyl ester – protected phosphonic acid group, showed that this compound could block the association of Grb2 with activated epidermal growth factor receptor (EGFR) in living cells and inhibit the growth of cells driven by PTK signaling through Ras (Gay et al., xref )."
reach
"8 The assay relies in the expression, in A549 EGFR biosensor cells (A549-EGFRB cells), of a SRC Homology 2 domain (SH2) of GRB2 that specifically binds to activated EGFR, fused to Green Fluorescent Protein (GFP)."
sparser
"A PLA developed to detect EGFR:GRB2 interaction was measured by quantitative immunofluorescence (QIF) using AQUA ® technology."
sparser
"We used the techniques of image correlation spectroscopy (ICS) and lifetime-detected Förster resonance energy transfer (also known as FLIM-based FRET or FLIM–FRET) to measure ligand-induced receptor clustering and Grb2 binding to activated EGFR in BaF/3 cells."
sparser
"Inducibility and quantification of EGFR-Grb2 interaction."
sparser
"The duration of the interaction between EGFR and GRB2 was defined as the time from their association to their subsequent dissociation."
sparser
"Phosphorylated EGF-R bound the adaptor protein, Grb2, and the EGF-R-selective tyrphostin, AG1478, blocked the C5b-9-induced ERK2 phosphorylation, [(3)H]AA release, and PGE(2) production by 45 to 65%, supporting a functional role for EGF-R kinase in mediating the activation of these pathways."
biogrid
No evidence text available
reach
"Grb2 binding to EGFR was suppressed, but EGF induced Shc tyrosine phosphorylation and Grb2 association with Shc were not significantly decreased."
sparser
"We also measured the interaction between EGFR and an adaptor protein, GRB2, which bridges the phosphorylated C-terminal region of the receptor and other cytoplasmic proteins."
sparser
"This is potentially due to "multi-state" interactions between intact receptors and adaptors, as suggested for EGFR-Grb2 interactions measured by single-molecule analysis [ xref ]."
sparser
"Thus, we have previously incorporated a photoreactive amino acid, -benzoyl--phenylalanine (Bpa; a), into the Src homology 2 (SH2) domain of the full-length GRB2 protein in mammalian cells and analyzed[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"A notable early example of FRET application to study endosomal signaling includes the visualization of the interaction between the EGF receptor (EGFR) and the signaling adaptor molecule Grb2 in membrane ruffles and on endosomes [ xref ]."
sparser
"It is therefore likely that tyrosine 1068 is the major site of interaction of EGF receptor with Grb2, although it is clearly possible that other sites could also play a role."
sparser
"Grb2 binding to EGFR was suppressed, but EGF-induced Shc tyrosine phosphorylation and Grb2 association with Shc were not significantly decreased."
sparser
"Those results fit the model of an increased retention time of Grb2 bound to the activated EGFR."
reach
"As NS5A did not appear to disrupt the interaction between c-Cbl, Grb2 and EGFR, we next assessed whether the effect on EGFR ubiquitination could be explained by the effects of NS5A on the interactions between the adaptor CMS and either EGFR or c-Cbl."
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."
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
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
"The Grb2 SH2 domain binds to Tyr1068 of EGFR and Tyr317 of Shc while its SH3 domains bind to mSos1."
sparser
"The Grb2 protein bound only to EGF-activated ErbB1 in this cellular system, and not to NRG-activated ErbB1 in a heterodimer with ErbB4."
sparser
"Although association of Grb2 with EGFR increased at a concentration of 100-μmol/L UTP compared with that with 25-μmol/L UTP ( Figure 1 ), it remained lower than when cells were stimulated with either [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
reach
"The cross linked Grb2 and EGFR complex was detected for 8 out 9 Grb2 mPyTK mutants; the D104mPyTK mutant gave the highest photo-cross-linking yield followed by the V105mPyTK, Q106mPyTK and N143mPyTK mutants (XREF_FIG b and Figure S10 in SI)."
sparser
"Epidermal growth factor receptor (EGFR) BRET structure-function studies identify the tyrosine residues 1068, 1114, and 1148 as the main residues mediating the interaction of EGFR with the adapter protein Grb2."
trips
"These analyses reveal a hierarchy of interactions between Grb2 and Shc with the EGFR and indicate that Grb2 can bind the tyrosine-phosphorylated EGFR directly, as well as indirectly via Shc."
reach
"Epidermal growth factor receptor (EGFR) tyrosine phosphorylation and recruitment of its adaptor proteins, Shc and Grb2, to EGFR were detected by immunoprecipitation and Western blot analysis."
reach
"Due to the optical diffraction limit of microscopy, the observed overlapping of fluorescent spots did not necessarily indicate direct interaction between EGFR and GRB2."
reach
"For example, after binding to EGFR, Grb2 recruits SoS1 (a Ras guanine nucleotide exchange factor) cell membrane localization, thereby activating the Ras/Raf/ERK signaling cascade XREF_BIBR, XREF_BIBR."
reach
"Owing to these attractive features, rsTagRFP has been used to monitor the interaction between epidermal growth factor receptor (EGFR) and growth factor receptor binding protein 2 (Grb2) in live cells by means of pcFRET with EYFP as a donor (XREF_FIG,)."
reach
"Here, we investigated how recruitment of Grb2 to EGFR is affected by the spatial organization and quaternary state of activated EGFR."
reach
"We therefore tested whether a phosphopeptide based on this sequence would be capable of influencing the interaction of EGF receptor and Grb2."
reach
"The biology behind the positive feedback loop in our example model is as follows [XREF_BIBR] : in response to growth factor stimulation, Gab1 is recruited to the plasma membrane through binding to the ErbB1 and Grb2 complex."
biogrid
No evidence text available
trips
"Results of co-immunoprecipitation experiments suggest that phosphotyrosines Y-1068 and Y-1173 mediate the binding of Grb2 to the EGFR."
sparser
"Here, we showed that a synthetic phosphopeptide encompassing the autophosphorylation site 1068 of EGFR formed a complex with endogenous Grb2 after this peptide was delivered into intact cells by a cell-permeable peptide import technique."
reach
"[49, 50, 51] Thus, we investigated whether SGCE loss changed the interaction between EGFR and the Cbl family or GRB2."
reach
"We were able to confirm the enrichment of the EGFR and Grb2 complex in CCPs."
sparser
"From these studies, we concluded that Grb2 binds directly to the EGFR at Y-1068, to a lesser extent at Y-1086, and indirectly at Y-1173."
reach
"Whereas Grb2 bound to Shc and EGFR in response to EGF, both Shc and Cbl were constitutively associated with the receptor."
reach
"Additionally, Grb2 and Shc also bind to the activated EGFR via their phosphorylated tyrosine residues, which then serve as an adaptor for the downstream Ras signaling and STAT signaling, respectively (XREF_FIG)."
sparser
"Ang II also increased the association of the adaptor protein Grb2 with the EGF-R. These findings indicate that Src and Pyk2 act upstream of the EGF-R and that the majority of Ang II-induced ERK phosphorylation is dependent on trans-activation of the EGF-R. Ang II-induced ERK activation in C9 cells is initiated by a PKCdelta-dependent but Ca(2+)-independent mechanism and is mediated by the Src/Pyk2 complex through trans-activation of the EGF-R."
sparser
"These analyses reveal a hierarchy of interactions between Grb2 and Shc with the EGFR and indicate that Grb2 can bind the tyrosine-phosphorylated EGFR directly, as well as indirectly via Shc."
reach
"Previous single-molecule measurements of the association between EGFR and GRB2 in vitro suggested that EGFR exists in multiple molecular states [32]."
reach
"Grb2 may bind to EGFR with or without Shc."
sparser
"The SH2 domain of GRB2 binds to the tyrosine auto- phosphorylation sites of activated EGF receptor [14], suggesting that the interaction of Sem-5 with Let-23 is direct."
reach
"We studied the effect of increasing doses of AG-1478 on the recruitment of Grb2 to EGFR and HER3 homo- and heteromers."
biogrid
No evidence text available
hprd
No evidence text available
sparser
"GRB2 binds the EGFR and contains one SH2 domain and two SH3 domains, which are crucial for IL3 signaling in hematopoietic stem and progenitor cell."
sparser
"To analyze the spatiotemporal regulation of EGFR-Grb2 interactions in living cells, we have combined imaging microscopy with a modified method of measuring fluorescence resonance energy transfer (FRET) on a pixel-by-pixel basis using EGFR fused to cyan fluorescent protein (CFP) and Grb2 fused to yellow fluorescent protein (YFP)."
sparser
"In addition, the precise mechanism regulating the α-LA-mediated disruption of the EGFR-Grb2 interaction must be explored in vivo ."
sparser
"This result suggests that in the context of a simple monomer/ N -mer equilibrium the cluster size of the Grb2-bound EGFR is approximately 4."
reach
"For example, it has been reported that Grb2 and Shc bind to activated EGFR via their phosphotyrosine residues and function as adaptors of downstream signaling."
reach
"Recruitment of the Adaptor Protein Grb2 to EGFR Tetramers."
sparser
"Demonstrating BRETs utility in this field, BRET studies helped identify tyrosine residues 1068, 1114, 1148 as the main residues mediating interaction of EGFR with Grb2 (Tan et al., xref )."
sparser
"As expected we found that EGF stimulated an association of EGF-R with Grb2, PRL, however, blocked this association."
sparser
"The functional consequence of Grb2 binding to the activated EGF receptor appears to be linked to the EGF- dependent accumulation of active (GTP-bound) Ras."
reach
"For example, the GRB2 adaptor protein binds activated EGFR at phosphorylated Tyr1068 XREF_BIBR, and phosphorylated Tyr1173 provides a docking site for the Shc scaffold protein, which is involved in mitogen activated protein kinase (MAPK) signaling activation XREF_BIBR."
biogrid
No evidence text available
reach
"Many of the model predictions exhibited a potential scale reduction factor of below 1.2 immediately after the " learning " period (e.g., ErbB1 expression, phosphorylated ErbB1, Grb2 bound to ErbB1, and phosphorylated Shc) while other predictions were unable to converge for the entire prediction window (e.g., phosphorylated PLC-gamma at times greater than 2 minutes)."
sparser
"By contrast, the binding of Grb2 to the EGFR was similar in both cell types."
sparser
"As Grb2 binding to the EGFR decreases, ligand-induced EGFR intracellular signaling also decreases [93] ."
reach
"For example, phosphorylation at Tyr 920 controls PI3K and Akt signaling through regulation of interactions of EGFR with p85, while phosphorylation at Tyr 1068 stimulates binding of EGFR with Grb2, which can trigger Ras and mitogen activated protein (MAPK) signaling XREF_BIBR."
reach
"To assay the interaction between EGFR and Grb2 in yeast, we used the intracellular domain of EGFR with L834R mutation as the membrane protein by fusing several types of lipidation motifs at both the N-terminus (Gpa1p motif; Gpa1N) and the C-terminus (Ras1p motif; Ras1C and Ste18p motif; Ste18C)."
sparser
"Therefore, we hypothesize that a single EGFR molecule can be simultaneously associated with functionally distinct Grb2 interaction partners during and after endocytosis."
sparser
"Interaction of EGFR and GRB2 correlates with active EGFR signaling and leads to activation of the MAPK/ERK pathway."
reach
"Direct Grb2 recruitment to EGF-R is not essential for EGF-R internalization in NIH3T3 and B82 cells [55-57]."
sparser
"Competition experiments with synthetic phosphopeptides corresponding to known autophosphorylation sites on the EGFR demonstrated that phosphopeptides containing Y-1068, and to a lesser extent Y-1086, were able to inhibit the binding of Grb2 to the EGFR, while a Y-1173 peptide did not."
sparser
"BaF/3 cells were stably transfected with fluorescently labeled forms of Grb2 (Grb2–mRFP) and EGFR (EGFR–eGFP)."
reach
"Meanwhile, it would not be possible to interconnect two events, ' Grb2 binds EGFR ' and ' Grb2 binds Shc ', from the sentence C without CR."
sparser
"Among these, the SHC adaptor protein was phosphorylated in absence of EGF, the other adaptor, GRB-2 was constitutively associated with the Glu627-EGF receptor in vivo and in vitro, and mitogen-activated protein kinase was constitutively phosphorylated."
hprd
No evidence text available
reach
"Accordingly, the estimated size of clusters containing Grb2 bound EGFR would be about 4.2 +/- 1 receptors and cluster and the estimated size of clusters free of Grb2 would be about 1.1 +/- 0.3 receptors and cluster."
sparser
"pcFRET made it possible to monitor EGFR-Grb2 interaction in the same cells at different time points before and after EGF stimulation."
reach
"In addition, RhoU is involved in EGFR mediated signaling, leading to AP1 transcriptional activity and cell migration in pancreatic cancer cells, events that require its interaction with the Grb2 and EGFR complex."
hprd
No evidence text available
reach
"Recruitment of SHC and Grb2 to EGFR elicits extracellular signal regulated kinase (ERK) activation XREF_BIBR - XREF_BIBR."
sparser
"Using NSCLC patient specimens and xenograft models, we have previously identified an association of EGFR:GRB2 complexes and response to EGFR inhibition [ xref ] and more recently identified a correlation between MET:GRB2 complexes and response to MET kinase inhibitors [ xref ]."
reach
"XREF_FIG b, the dose- and time dependent increases in Grb2 SH2 binding to EGFR were obvious both by far-Western (~ 180 KDa band on upper panel) and SH2-PLA (Ct value in lower panel)."
reach
"For example, it would not be possible to extract the correct event, ' Grb2 binds EGFR ', from the sentence A in XREF_FIG without coreference."
reach
"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."
reach
"Although GRB2 binds to the EGF receptor and the PDGF #-receptor, it does not become tyrosine phosphorylated in response to 48 L. Claesson-Welsh ligand stimulation."
reach
"In contrast to the activated epidermal growth factor receptor that binds the GRB2 and 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
"For example, growth factor receptor-bound protein 2 (GRB2) binds activated EGFR at phospho-Tyr1068, which is crucial to the EGF-induced activation of Ras signalling pathway ( xref )."
sparser
"These studies indicate that the functional consequence of association of the activated EGF receptor with Grb2 is accumulation of active Ras."
biogrid
No evidence text available
biogrid
No evidence text available
reach
"Sorkin and co-workers previously established that FRET can be used to detect interactions between EGFR and Grb2, but no estimates of cluster sizes were made in that study."
reach
"Hence, Grb2 binds directly, and indirectly via Shc, to the activated EGF receptor."
reach
"It has been shown that EGF activated EGFR interacts with Grb2 at plasma membrane and in endosomes."
reach
"Further studies showed that PD153035, which does not reverse ligand induced EGFR down-regulation, blocks EGF induced EGFR activation as well as EGFR 's binding to c-cbl and Grb2."
sparser
"In summary, the results of this study demonstrate that α-LA, a novel antioxidant, targets the EGFR-Grb2 interaction and inhibits EGFR-MAPK/ERK signaling in NSCLC cell lines, enhancing the effect of EG[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
reach
"The SH2 sites of Grb2 can bind phosphotyrosine-1068 of ErbB1 (monomer or dimer) (interaction-9), and the SH3 site of Grb2 can bind cytosolic SOS (interaction-12)."
biogrid
No evidence text available
reach
"The Binding of Shc1 and Grb2 to EGFR Phosphosites Can Be Enchanced by Sequence Changes That Would also Increase Phosphorylation by c-Src."
reach
"GRB2 is required for survival of cells with mutant EGFR [XREF_BIBR] and the interaction between EGFR and GRB2 is abrogated by erlotinib, resulting in loss of downstream ERK signaling [XREF_BIBR, XREF_BIBR]."
reach
"Moreover, cell lines with increased EGFR : GRB2 PLA signal had increased abundance of Tyr 1068 phosphorylated EGFR (XREF_FIG) and a robust interaction between EGFR and GRB2 as determined by coimmunoprecipitation (XREF_FIG)."
sparser
"Unlike the EGF receptor and other receptors that bind to Grb2 directly, FGF receptors do not bind directly to Grb2 upon FGF stimulation."
reach
"As depicted in Fig. 1 (pathway a), it is now known that activated EGF receptor binds the adaptor protein Grb2 through an interaction between autophosphorylated tyrosine on the receptor and the SH2 dom[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
reach
"Our immunoprecipitation results indicate that there are enhanced interactions between EGFR and Ras and EGFR and Grb2 after both 3- and 14-days."
reach
"Our adaptive signaling model is supported by recent work using phosphoproteomic approaches, which demonstrated that GRB2 was bound to EGFR in unperturbed ALK+ lung cancer cells and that EGFR phosphorylation increased in response to crizotinib treatment."
sparser
"The Src homology 2 domain-containing protein Grb2 binds to the tyrosine-phosphorylated ErbB1 molecule and activates at least three signalling pathways, Ras-Raf-MEK-ERK, phosphoinositide 3-kinase (PI3K)-AKT, and JAK-STAT signalling pathways, for cell proliferation, survival, and migration, and their continuous abnormal activation eventually leads to cancer cell tumourigenesis, invasiveness, and metastasis xref – xref , xref – xref ."
biogrid
No evidence text available
sparser
"On and off rates for the EGFRGrb2 interaction were measured, with three states being observed."
sparser
"The calculated rate constants showed that EGF facilitated the associations of GRB2 with EGFR."
bel
"Epidermal growth factor (EGF) stimulates recruitment of RN-tre to the EGF receptor (EGFR) in a Grb2-dependent manner."
reach
"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_BIBR]."
sparser
"EGFR is able to activate PI3K through a series of reactions: active EGFR binds adaptor protein Grb2, which recruits the docking protein Gab1, which contains pYXXM motifs to which SH2 domains on the regulatory subunit of PI3K (p85) bind, thereby bringing the catalytic subunit of PI3K (p110) in proximity to its membrane-bound lipid substrates [ xref ]."
reach
"Grb2, which is constitutively associated via its SH3 domain with Grb2 associated binder 1 (Gab1), binds to the EGFR."
reach
"In response to EGF receptor activation and autophosphorylation, the Grb2 and Sos complex binds to the EGF receptor, recruiting Sos to the plasma membrane where Ras protein is located."
sparser
"The results of the intracellular domain of EGFR and Grb2 interaction showed that our Gγ recruitment systems could be exploited as a convenient heterologous system to discern the strong binders to the phosphotyrosines in the intracellular domain of EGFR, and therefore would provide the basis for studying other receptor tyrosine kinases as well."
sparser
"GRB2 primarily associated with immobile EGFR dimers and trimers ( Fig. 4 F)."
reach
"Third, the EGFR exon 25-26 deletion mutation identified in lung cancer increased colony formation in soft agar and the interaction between EGFR and Grb2 similar to what was observed with the C1025A mutant."
reach
"Notably, components of the EGF signaling network, Adam10, a metallopeptidase that processes EGF, and Grb2, an adaptor protein that binds directly to the EGF receptor, exhibited a greater importance for transgenic than for tumor TFs (XREF_FIG, blue dots)."
sparser
"The SH2 domain of Grb2 may bind to the auto phosphorylation site Y1068 of the EGF receptor, and the SH3 domains of Grb2 may bind to the carboxy-terminal domain of Sos."
sparser
"Furthermore, Western blotting of Grb2 immunoprecipitates with anti-EGFR showed that Grb2 was bound to the EGFR in response to EGF (Fig. 8D)."
reach
"Hence, in response to EGF- 274 receptor autophosphorylation, a pre- existing Grb2 and Sosl complex binds to the EGF receptor, recruiting Sos to the plasma membrane where the Ras pro- tein is located."
sparser
"Results of co-immunoprecipitation experiments suggest that phosphotyrosines Y-1068 and Y-1173 mediate the binding of Grb2 to the EGFR."
reach
"Phosphorylation of EGFR Y1068 leads to GRB2 binding to EGFR which can increase downstream signalling of MEK and MAPK pathway."
biogrid
No evidence text available
reach
"The EGFR and GRB2 complex adopts multiple conformations, as demonstrated in a previous in vitro study [32]."
biogrid
No evidence text available
sparser
"We present a method that allows us to quantify the stoichiometry and the association constant of the EGFR-Grb2 binding interaction in the plasma membrane, in the presence and absence of activating ligand."
sparser
"In another study, they combined micro-patterned surfaces with TIRFM to measure the interaction of growth factor receptor-bound protein 2 (Grb2) with EGFR [ xref ]."
sparser
"c-CBL is also recruited to EGFR through an adaptor protein, GRB2 which binds to phosphorylated tyrosine sites on EGFR (mainly Y1068 and Y1086) promoting ubiquitination and degradation of this receptor[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
reach
"By contrast, the binding of Grb2 to the EGFR was similar in both cell types."
sparser
"These interactions between EGFR and Grb2 were detected based on the colocalization of fluorescent spots."
reach
"Efficient energy transfer between CFP and YFP should only occur if CFP and YFP are less than 50A apart, which requires direct interaction of the EGFR and Grb2 fused to these fluorescent moieties [3]."
sparser
"This basic interaction between Grb2 and EGFR appeared without any additional EGFR activation and may be caused by the stimulating nature of the antibody coated surface and/or the presence of growth factor containing serum."
biogrid
No evidence text available
biogrid
No evidence text available
sparser
"The association of GRB2 to the EGFR was not augmented in the transgenic mice as shown in xref ."
sparser
"To study the mechanism of receptor activation in greater detail we examined activation mediated Grb2 binding to the EGFR mutants."
biogrid
No evidence text available
reach
"GRB2 can bind the epidermal growth factor receptor (EGFR), and Daly et al. [XREF_BIBR] reported it to be associated with breast cancer."
sparser
"Foremost among these is the Ras/Raf/mitogen-activated protein kinase (MAPK) pathway, in which the adaptor protein Grb2 binds to phosphorylated tyrosine residues of EGFR, thus activating the Son of sevenless protein. xref This protein in turn activates the G-protein Ras, which initiates a cascade of phosphorylation of MAPKs, which are specific serine/threonine kinases."
biogrid
No evidence text available
reach
"Grb2 bound EGFR clusters were dispersed at an average of 11 clusters and mum 2, whereas the Grb2-free EGFR population had a spatial organization characterized by an average cluster density of 17 clusters and mum 2."
sparser
"FRET–FLIM–ICS Measurements Reveal That Grb2 Is Associated with Higher-Order EGFR Clusters."
biogrid
No evidence text available
reach
"However, the interaction of EGFR and Grb2 can be clearly stimulated; the addition of EGF resulted in a prominent increase of the Grb2-YFP fluorescence within EGFR enriched mu-patterns."
reach
"Based upon parameter fitting, we estimated that the association (k on) and dissociation (k off) rate constants between Grb2 and EGFR are 0.0072 (nM x s) -1 and 9.34/s, respectively."
sparser
"2,19,22 Binding affinity was assessed by an ELISA-type assay that measures the ability of a compound to inhibit the binding of the phosphorylated C-terminal [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
biogrid
No evidence text available
sparser
"Following activation of EGFR, the SH2 domain of Grb2 can bind to the EGFR either directly (via Y1068 and Y1086) or indirectly via tyrosine phosphorylated Shc (Sasaoka et al., xref )."
reach
"The adaptor protein Grb2 (growth factor receptor binding protein 2) binds to EGFR, which leads to activation of Stat3 pathways [XREF_BIBR]."
reach
"Another EGFR binding adaptor protein is growth factor receptor bound protein 2 (Grb2), which binds activated EGFR through its Src homology 2 (SH2) domain XREF_BIBR."
biogrid
No evidence text available
hprd
No evidence text available
sparser
"In this study, we generated fusion proteins containing one or two Src-homology 2 (SH2) domains of growth factor receptor bound protein 2 (Grb2), which bind to phosphorylated EGFR, added with HIV-1 transactivating transcription for cell membrane penetration (termed TSF and TSSF, respectively)."
sparser
"We have observed the interaction between GFP-tagged EGFR and a cytoplasmic protein GRB2 that had been tagged with TMR-labeled Halo protein in living cells."
sparser
"To explore the translational application of SH2-PLA, we analyzed binding of Grb2 SH2 to EGFR in lung cancer patient tissues."
sparser
"We therefore tested whether a phosphopeptide based on this sequence would be capable of influencing the interaction of EGF receptor and Grb2."
biogrid
No evidence text available
sparser
"The EGF receptor binds Grb2 directly, and its Grb2-binding sites are also required for recruitment of Gab1 ( xref ; xref ); thus, the EGF receptor may recruit Gab1 via Grb2-Gab1 complexes."
sparser
"However, weakly phosphorylated EGFRvIII can still associate with Grb2, and hence indirectly associate with CBL."
sparser
"In streptolysin O permeabilised cells, a tyrosine phosphopeptide, EGFR-Y1068P, which binds to the SH2 domain of Grb2, totally blocks growth factor induced formation of complexes between Grb2 and Shc or EGF receptor, and also blocks activation of nucleotide exchange on Ras."
reach
"The activated EGF receptor forms a complex with the adapter proteins, Shc and Grb2, thereby recruiting Sos, the GDP-GTP exchanger for Ras."
reach
"Similarly, we recently isolated UbVs that bound specifically to the human epidermal growth factor receptor 3 (HER3) and the growth factor receptor-bound protein 2 (Grb2) and showed that UbVs acted as potent antagonists of Grb2-mediated cell signalling (Leung, Jarvik, & Sidhu, 2017)."
sparser
"While the proliferation assay and simulations report results in different units, it is notable that the maximum in the formation of the ErbB1-Grb2 plus ErbB1-Shc complexes and cell proliferation corresponded to the same dose of EGF."
sparser
"Cbl was basally associated with the adaptor protein growth factor receptor-binding protein 2 (Grb2), and this interaction was further enhanced by EGF stimulation; however, the interaction was entirely mediated via the Grb2 Src homology 3 (SH3) domains, suggesting that binding of Grb2 SH2 domain to EGF receptor provides one mechanism of Cbl's association with the EGF receptor."
sparser
"After treatment with EGF, cell-free extracts were produced and the ability of phage-derived peptides to inhibit the interaction between the EGFR and the GRB2 protein was examined by means of an immuno[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"CCPs represent the main structures for the endocytosis of activated EGFRs xref , and the interaction of Grb2 with the EGFR plays a decisive role in the initial steps of clathrin-mediated internalization xref , xref ."
biogrid
No evidence text available
sparser
"Interestingly, the relatively rapid kinetics of EGFR-GRB2 binding, xref which may not prevail for all EGFR adaptors, produces EGFR-GRB2 complex sensitivity results that are indistinguishable from those for phosphorylated receptor ( Supplementary Figure S2a–d )."
reach
"Mechanistically, AT 1 R mediated ERK1/2 activation was dependent on G q/11 and EGFR tyrosine kinase activity, whereas the recruitment of Grb2 to the EGFR was independent of G q/11 and only partially dependent on EGFR tyrosine kinase activity."
sparser
"Earlier work has shown that the signaling activity of EGFR is potentiated in endosomes, as judged by a high stoichiometry of Grb2 binding to EGFR [ xref ]."
sparser
"But in this schema, the designer gives some abbreviations like “EGFR-GRB2 (Epidermal Growth Factor Receptor- Growth Factor Receptor Bound Protein 2)” which does not included in the dictionary."
bel
"The dimerization of two EGFR family molecules leads to phosphorylation of C-terminal tyrosine residues either by autophosphorylation or by a SRC-related kinase followed by binding of GRB2, a RAS adaptor protein, at the SH2 domain of the receptor; binding of the proline-rich C-terminus of SOS, a guanine nucleotide exchange factor, to the SH3 domain of the receptor; exchange of a GTP from the receptor complex for a GDP from the RAS protein to form activated RAS; activation of phosphatidylinositol-3-kinase (PI-3 kinase) to initiate signaling by the biochemical pathways that are triggered by diacylglycerol production and protein kinase C activation; and activation of the series of cytoplasmic serine and threonine kinases beginning with RAF to initiate signaling by the biochemical pathways that are triggered by members of the MAPK family (e.g. ERK 1 and 2). EGFR signaling also activates other pathways in the cell including the Janus kinase (JAK)/signal transduction activators of transcription (STAT) pathways [80, 81]."
reach
"The results of the intracellular domain of EGFR and Grb2 interaction showed that our Ggamma recruitment systems could be exploited as a convenient heterologous system to discern the strong binders to the phosphotyrosines in the intracellular domain of EGFR, and therefore would provide the basis for studying other receptor tyrosine kinases as well."
reach
"In agreement with the autophosphorylation data, c-Cbl and Grb2 interact strongly with EGFR homodimers, and poorly with EGFR : HER2 heterodimers (XREF_FIG)."
sparser
"The PLA to detect EGFR-GRB2 interaction was unrelated to overall EGFR expression or mutation in a series of patients with NSCLC with known mutation status."
reach
"Interestingly, direct Cbl binding to pTyr1045 appears to play a minor, if any, role in the CME of EGFR, whereas Grb2 mediated interaction with EGFR is critical [XREF_BIBR]."
reach
"The average value of 4 +/- 1 EGFR 's per EGFR and Grb2 complex from the FRET-FLIM-ICS experiments is in excellent agreement with the model prediction that the EGFR tetramer is the dominant Grb2 bound form, whereas the dominant Grb2-free form is the monomer, which also agrees well with the cluster size estimate of 1 +/- 0.3 EGFR 's from the cell averaged data."
biogrid
No evidence text available
reach
"The binding of Cbl and Grb2 to EGFR depended on protein concentrations and binding affinities : protein concentrations were carefully measured, while binding affinities were indirectly determined by fitting ubiquitination dose response curves under various experimental conditions, within well defined experimental constrains taken from published studies (XREF_SUPPLEMENTARY)."
reach
"EGF induced phosphorylation of ERK was enhanced in necdin-null CPCs, where the interaction between EGFR and the adaptor protein Grb2 was strengthened, suggesting that endogenous necdin suppresses the EGFR and ERK signaling pathway in CPCs."
reach
"Subsequently, lipocortin-1 competitively inhibited Grb2 binding to EGFR, thereby blocking the recruitment of critical signaling molecules necessary for EGF actions [XREF_BIBR]."
reach
"A marked reduction in the GRB2 and EGFR complex and absence of SOS-EGFR were observed in PC-9/ZD cells, even though the protein levels of GRB2 and SOS in PC-9 and PC-9/ZD cells were comparable."
reach
"The duration of the interaction between EGFR and GRB2 was defined as the time from their association to their subsequent dissociation."
reach
"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_BIBR]."
reach
"Cluster distribution at 10nM EGF shows nearly 95% of the EGFR tetramers containing at least one bound Grb2, while monomers, dimers, and trimers are predominantly (~ 98%) free of Grb2."
reach
"Although a selective EGFR kinase inhibitor completely abolished Ang II induced recruitment of Grb2 to EGFR and markedly attenuated Ang II induced ERK activation, it had no effect on Ang II induced PYK2 tyrosine phosphorylation or its association with c-Src and Grb2."
reach
"On top, the Sf21 microsomes functionalized with receptor molecules represent an ideal platform for structural and functional in vitro studies as exemplified by investigation of the EGFR and Grb2 interaction."
sparser
"Furthermore, it has been shown that when quiescent cells are stimulated with epi- dermal growth factor (EGF), Grb2 rapidly binds to the phosphorylated EGF receptor."
biogrid
No evidence text available
biogrid
No evidence text available
sparser
"EGF-induced phosphorylation of ERK was enhanced in necdin-null CPCs, where the interaction between EGFR and the adaptor protein Grb2 was strengthened, suggesting that endogenous necdin suppresses the EGFR/ERK signaling pathway in CPCs."
sparser
"The model is an extension of our earlier model xref and now includes EGFRGrb2 binding in addition to the processes considered in the original model (i.e., ligand–receptor binding, self-interactions capable of mediating receptor oligomerization, and receptor autophosphorylation)."
sparser
"Efficient energy transfer between CFP and YFP should only occur if CFP and YFP are less than 50A apart, which requires direct interaction of the EGFR and Grb2 fused to these fluorescent moieties [3]."
reach
"Epidermal growth factor receptor pathway substrate 8 (EPS8)/related to the N-terminus of tre oncogene (RN-TRE) and growth-factor receptor bound protein 2 (GRB2)/Ras and Rab interactor 1 (RIN1) have been reported to coordinate the function of Rab5 GEFs and GTPase activating proteins (GAPs) for the maintenance of normal trafficking of cell membrane receptors."
reach
"SHP2 is also relevant to the crosstalk between TGFbeta and EGF signaling during EMT, as EGF activates SHP2 activity by recruitment of the adaptor protein GAB1 to the EGF receptor and Grb2 complex [XREF_BIBR]."
sparser
"In two series of patients with lung adenocarcinoma, the PLA to detect EGFR-GRB2 interaction was independently associated with longer survival (hazard ratio = 0.46, 95% confidence interval: 0.2-0.78, p = 0.0085 and hazard ratio = 0.48, 95% confidence interval: 0.2-0.85, p = 0.017)."
sparser
"Grb2-bound EGFR clusters were dispersed at an average of 11 clusters/μm 2 , whereas the Grb2-free EGFR population had a spatial organization characterized by an average cluster density of 17 clusters/μm 2 ."
reach
"The multifunctional Grb2 adapter protein binds the EGFR at phospho-Tyr1068 once the EGFR is activated [XREF_BIBR]."
reach
"As shown in Figure XREF_FIG, GSTP1 and GRB2 could be detected in the immunoprecipitation complex of phospho-EGFR antibody in 30 ng/mL EGF stimulated CNE2 cells, and could not be detected by the pretreatment of the cells with 1 mum EGFR inhibitor PD153035, which indicates that GSTP1 and GRB2 can interact with phospho-EGFR, are downstream targets of EGFR signaling pathway."
reach
"After EGF stimulation, the Grb2 SH2 domain binds to the EGF receptor directly or indirectly through proteins such as Shc, FAK, Syp, and IRS-1, by recognizing phosphotyrosine (pTyr)-containing sequences."
reach
"We first examined the adaptor protein, Growth factor receptor bound protein 2 (Grb-2), which contains an SH2 domain and two SH3 domains and can directly bind the EGFR XREF_BIBR."
hprd
No evidence text available
reach
"Primary epithelial cells, HCLEs, and endothelial cells (PAEs) infected with the wild-type EGFR (E1-PAE) were stimulated with media change (control), injury (w), UTP, or EGF to determine recruitment of[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
reach
"We also show that the truncated EGF receptor constitutively associates with the adapter proteins Shc and Grb2 which are involved in the recruitment of Ras to activated receptors."
sparser
"However, mutation of C1025 has the strongest increas in the binding of EGFR with the adapter protein Grb2."
reach
"Recruitment of Grb-2 to the EGFR is important for plasma membrane recruitment and consequent tyrosine phosphorylation of the scaffolding protein, Grb2-associated-binding protein 1 (Gab-1) XREF_BIBR."
reach
"Together, these results suggest that the EGFR and Grb2 complex is required for the LPS induced activation of NRas and LPS induced cholangiocyte expression of the proinflammatory mediator, IL6."
sparser
"To assay the interaction between EGFR and Grb2 in yeast, we used the intracellular domain of EGFR with L834R mutation (EGFR L834R,cyto ; that is constitutively dimerized and activated even in the absence of EGF xref xref ) as the membrane protein by fusing several types of lipidation motifs at both the N-terminus (Gpa1p motif; Gpa1N) and the C-terminus (Ras1p motif; Ras1C and Ste18p motif; Ste18C)."
reach
"56 To conclude, EGFR higher-order oligomers bind Grb2 and therefore should be considered, along with the classical EGFR dimer, in models of EGFR signaling."
reach
"This resulted in increased binding of another adaptor protein Grb2 to the Src and EGFR complex and the subsequent activation of Ras and MAPKs."
reach
"Third, the distribution and proportion of Grb2 bound EGFR oligomers revealed by theoretical modeling indicated a predominance of the EGFR tetramer as the major Grb2 bound form."
reach
"We developed a PLA to measure the interaction between EGFR and GRB2."
reach
"This binding surface is responsible for the specificity of each SH2 and for the preferential binding of GRB2 to peptides containing the phosphorylated Tyr-X-Asn-X motif.14 This Tyr-X-Asn-X sequence is[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"EGFR and GRB2 interaction, correlates with active EGFR signaling and leads to activation of MAPK/ERK pathway."
reach
"With the opposite BRET orientation, HER3 truncation means that Grb2 and Venus can only bind to EGFR in the HER3trunc, Rluc8, and EGFR complex, which results in less donor-acceptor proximity than binding to HER3 and Rluc8."
sparser
"Binding of GRB2 to the p-EGFR Tyr1068 is crucial to the EGFR-induced MAPK signaling pathway [ xref ]."
reach
"With this approach, we confirm the previously characterized interaction between Grb2 and the EGF receptor, and we identify novel partners of the IGF-1 receptor and of the JAK proteins."
sparser
"Moreover, the positive correlation between clustering of EGFR and EGFRGrb2 interaction is consonant with the concept that the nonrandom spatial organization of receptor dimers, in our case, tetramers, can concentrate signaling complexes in space and time."
sparser
"Shc bound to pEGFR associates with growth factor receptor-bound protein 2 (Grb2), while Grb2 can directly associate with pEGFR [ xref , xref ]."
sparser
"In contrast, after EGF addition, Grb2-rsTagRFP photoswitching resulted in a striking and reversible ~20% modulation of the EGFR-EYFP fluorescence both at the plasma membrane and on endosomes, strongly suggesting the occurrence of pcFRET due to the EGFR-Grb2 interactions at these locations."
reach
"Recruitment of the EGFR together with Grb2 to clathrin coated pits (CCPs) was found to be a key feature in our assay."
sparser
"The multifunctional Grb2 adapter protein binds the EGFR at phospho-Tyr1068 once the EGFR is activated [ xref ]."
sparser
"Finally, the assay provides additional biological insight: for the present study we used the μ-patterning approach for a quantitative analysis of the EGFR-Grb2 interaction."
sparser
"A PLA developed to detect EGFR-GRB2 interaction was measured by quantitative immunofluorescence using Automated Quantitative Analysis technology."
reach
"Thus, under the experimental conditions described here, indirect recruitment of Grb2 or CIN85 to the EGF-R (via binding of their SH3 domains to proline rich motifs in the C-terminal half of Cbl) is di[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"Using a proximity ligation assay, Smith and colleagues recently showed that in 25% of surgical specimens collected from NSCLCs harboring a KRAS mutations, EGFR associates with the growth factor receptor–bound protein 2 (GRB2) [ xref ]."
sparser
"In addition, EGF receptor (Tyr992) induces PKC-dependent ERK 1/2 phosphorylation via PLCγ ( xref ); EGF receptor (Tyr1068) associates with the adaptor Grb2, which is the main step in EGF receptor-dependent induction of RAS/MAPK ( xref )."
biogrid
No evidence text available
sparser
"The adaptor protein Grb2 (growth factor receptor-binding protein 2) binds to EGFR, which leads to activation of Stat3 pathways [ xref ] ."
sparser
"As depicted in Fig. 1 (pathway a), it is now known that activated EGF receptor binds the adaptor protein Grb2 through an interaction between autophosphorylated tyrosine on the receptor and the SH2 d[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"2A and 3 A), we validated whether the EGFR-Grb2 interaction is involved in the α-LA-induced reduction of cell proliferation."
reach
"Of greater importance, we further show that RhoU is also capable of synergizing with activated EGFR in JNK and AP1 mediated transcriptional activity in a manner dependent on SH3 binding, as the DM RhoU, which is physically uncoupled from GRB2 and EGFR complex, is unable to synergize with activated EGFR in either JNK and AP1 activation or increased cell motility."
sparser
"It reduces the level of EGFR (ERBB)-receptor expression [ xref ] and inhibits binding of GRB2 to EGFR (Figure xref )."
sparser
"These values were assessed by an ELISA-type assay that measures their ability to inhibit the binding of the phosphorylated carboxy-terminal intracellular domain of the epidermal growth factor recepto[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
sparser
"Interaction between activated EGFR and Grb2 at the endosomes upon EGF stimulation was proven by FRET microscopy [5] ."
reach
"Activated EGFR or HER family members bind to Grb2 and Sos, resulting in the activation of the Ras and Raf pathway and phosphorylation of mitogen activated protein kinases (MAPK) [XREF_BIBR - XREF_BIBR]."
sparser
"We found EGFR bound to GRB2, suggesting how EGFR signaling can control this network and drive resistance to ALK TKI by facilitating EGFR:GRB2 signaling complexes."
sparser
"Here, we seek to characterize the interaction between epidermal growth factor receptor (EGFR) and the cytoplasmic adaptor protein growth factor receptor-bound protein 2 (Grb2) in a cellular context."
sparser
"Unlike the tyrosine phosphorylation and Grb2 interaction with the EGFR, repeated peroxide exposure (at R4 response point) did not significantly affect Pyk2 Tyr-881 phosphorylation (Figures xref and xref ) or the Grb2 content of the Pyk2 immunoprecipitates (Figures xref and xref )."
reach
"Grb2 can bind EGFR directly or through another SH2 containing protein, Shc."
biogrid
No evidence text available
reach
"It reduces the level of EGFR (ERBB)-receptor expression [XREF_BIBR] and inhibits binding of GRB2 to EGFR."
reach
"42 Such a mechanism might also account for the observation that Grb2 bound EGFR is in a higher-order oligomeric complex relative to Grb2-unbound EGFR and for the positive correlation between Grb2-mRFP binding and EGFR-eGFP clustering."