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EGF binds EGFR. 1000 / 4803
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"Furthermore, M2 TAMs secrete Epidermal Growth Factor (EGF) (Zeng et al., 2019; Wu et al., 2020b), which binds to EGFR on cancer cells, for activating their growth signaling including MAPK/ERK (Liang et al., 2022) and PI3K/Akt pathways (Zhang et al., 2021b), promoting cell motility and invasion (Haque et al., 2019; Zeng et al., 2019; Onal et al., 2021)."
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"In this paper, taken into consideration abovementioned differences, we have focused on the behavior of vesicles bearing EEA1 and have demonstrated that (i) these vesicles are detected in HeLa and A549 cells in absence of external growth factors; (ii) the level of membrane associated EEA1 did not change after stimulation of endocytosis with EGF and formation of comparable number of EGF and EGFR loaded vesicles; (iii) newly formed endocytic vesicles loaded with EGF and EGFR complexes directly fuse with pre-existing EEA1 positive vesicles forming hybrid structures with domain organization of united membrane, (iv) fusions results in effective increase of EGFR- positive domains area, that makes it possible to form ILVs and sort there EGF and EGFR."
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"Indeed, in early reports it was shown by means of EM that transferrin or BSA and EGF and EGFR complexes can be found in the same early tubulovesicular structures, but with time the latter become redistributed from the outer endosomal membrane to ILVs thus decreasing the possibility of EGFR recycling [XREF_BIBR, XREF_BIBR]."
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"On fixed cells we demonstrated that EE vesicles contact each other with EEA1 domains, however live cell imaging of PAE A11 cells shows that it is not so easy for two endosomes to fuse : their behavior resembles a kind of dance, when two vesicles come close but fail to fuse, then go apart, than return back and finally fuse with one of them throwing towards the other a membranous protrusion, free of active EGF and EGFR complexes."
sparser
"SPR analysis confirmed a high-affinity interaction between EGF and EGFR (26.1 nM, xref ), with Trichoharzin significantly inhibiting this interaction in a concentration-dependent manner, reducing the binding affinity of EGF to EGFR to 191, 372, and 1740 nM at concentrations of 125, 250, and 500 μM, respectively ( xref )."
sparser
"Cetuximab is a chimeric mouse-human immunoglobulin G (IgG) 1 monoclonal antibody (mAb), which can target the extracellular domain of the epidermal growth factor receptor (EGFR) and competitively inhibit the binding of EGFR to ligands such as epidermal growth factor, thus blocking the downstream signal transduction to exert antitumor effects. xref Additionally, cetuximab is an immunomodulating agent that promotes T-cell infiltration into the CRC TME and upregulates ICIs. xref The mechanisms of the anti-tumor effects of cetuximab are depicted in xref , which mainly include: (1) Increased levels of cyclin-dependent kinase inhibitory proteins p21 and p27 and decreased levels of cyclin D1, inhibiting tumor cell proliferation, xref (2) downregulated expression of the apoptosis suppressor B-cell lymphocyte-2 gene and upregulated expression of the proapoptotic Bcl-2-associated X protein gene, activating caspase-8 to induce apoptosis in tumor cells through the caspase cascade reaction, xref and (3) simultaneous binding of cetuximab to the corresponding antigen via its allosteric fragment crystallizable (Fc) segment that binds to the Fc receptors of effector cells (such as natural killer [NK] cells, neutrophils, macrophages, and platelets) to kill tumor cells through antibody-dependent cell-mediated cytotoxicity (ADCC). xref "
sparser
"EGFR , one of the members of the epidermal growth factor receptor family ( xref - xref ), specifically binds to ligands such as epidermal growth factor, transforming growth factor, bidirectional regulating protein, B cell factor, liver-binding EGF-like growth factor, and epidermal regulation factor ( xref , xref )."
sparser
"3D classification of EGF-EGFR revealed multiple, closely-related conformational states of the ligand-bound ectodomain, in which a "scissor-like" rotation of the EGF binding portion of the ectodomain (D1-3) was correlated with a separation of the ends of the membrane-proximal domain (D4); the larger the scissor angle (~25{degree sign}), the closer the ends of D4 (~5 Å), and vice versa."
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"However, conflicting structural models have been proposed for the architecture and stoichiometry of EGF bound EGF receptor multimers : one model involves self association of ligand bound dimers, while another model involves association via unoccupied ligand binding sites, resulting in oligomers that can bind two EGF molecules at most."
sparser
"The authors determined cryo-EM structures with TGFalpha bound to EGFR and found that, in this ensemble of structures, D4 in the tips-separated conformation was destabilized (vs. in the EGF-EGFR structures) because of slight differences in the ligand-binding head of EGFR induced by TGFalpha vs. EGF binding."
sparser
"Binding between EGF and EGFR forms a dimer that is phosphorylated or transphosphorylated to produce biological signals, then activating several downstream signal transduction pathways and transducing them inside cell nuclei. xref It has previously been reported that EGFR is highly expressed in malignant tumors instead of in normal tissues. xref Similarly, the observation group herein had significantly higher percentage and positive rate in EGFR expression than those of the control group (P<0.05)."
sparser
"Epidermal growth factor receptor (EGFR) binds to epidermal growth factor (EGF) and also to transforming growth factor α (TGF α ), leading to activation of the receptor which homodimerizes with a family of proteins including human epidermal growth factor receptor 2 (ERBB- 2), human epidermal growth factor receptor 3 (ERBB-3) and human epidermal growth factor receptor 4 (ERBB-4). xref This type of activation induces activity of tyrosine kinase domains, resulting in phosphorylation and recruitment of proteins such as Son of sevenless (SOS) which in turn activate Rat sarcoma virus (RAS). xref , xref "
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"A study reported that although EGF and TGF-alpha bind the EGFR with similar affinities at relatively neutral pH (7.4), a drop in pH to 6 (to mimic acidification in EEs) led to the dissociation of TGF-alpha from the EGFR that allowed the receptor to be recycled back to PM, whereas the EGF and EGFR complex remained stable and led to its trafficking to degradation components [XREF_BIBR]."
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"Normal mode analysis of both structures indicated that the binding pocket of EGFR exhibits a significantly higher mobility in Ten14 and EGFR complex compared to that of the EGF and EGFR complex; we hypothesized this may be attributed to loss of key high-affinity interactions within the Ten14 and EGFR complex."
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"The EGFR binding site was determined from the EGF-EGFR complex, retrieved from the Protein Data Bank (PDB code 3NJP [56]) (Figure 2A) and chosen to perform peptide-protein recognition of 01_cys EGFR and 06_cys EGFR (amino acid residues: 12–18, 29, 90–100, 346–360, 384, 409, 465–468)."
sparser
"However, we previously found that the addition of 10 nM EGF (effectively saturating concentration, since the effective EGF-EGFR dissociation constant is ~1 nM ( xref )) decreased the FRET efficiencies to the point that the hetero-FRET straddled the proximity FRET line (red symbols in xref )."
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"Each member has distinct binding affinities to different ligands that allows the classification of ligands into three groups : in the first group, EGF, transforming growth factor-alpha (TGF-alpha) and amphiregulin (AREG) specifically bind to EGFR; in the second group, betacellulin, heparin binding EGF (HB-EGF) and epiregulin bind to both EGFR and ERBB4; the third class include neuregulins (NRGs) that bind to either only ERBB4 (NRG3 and NRG4) or both ERBB3 and ERBB4 (NRG1 and NRG2)."
sparser
"Dhc64C, a microtubule motor protein homologous to human cytoplasmic dynein heavy chain1, has been shown to interact genetically with EGF receptor and EGF ligand trafficking [ xref ]. mys gene codes for integrin beta-PS protein which has been extensively studied and its role in development of myotendinous system is well established in Drosophila as well as vertebrates [ xref , xref , xref , xref , xref ]."
sparser
"Since Roovers et al. reported (i) an inhibition of EGF-mediated EGFR phosphorylation in the presence of the EGFR-specific Nb 7D12 [ xref ], and (ii) also mentioned a blockage of EGF binding by the Nb 7C12 used in our studies [ xref ] we analyzed the capability of our α-EGFR TMs to mediate EGFR signaling and blocking of EGF binding to EGFR."
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"For example, it has been shown or suggested that EGCG can inhibit EGFR tyrosine kinase activity (IC 50 = 1-2 muM) XREF_BIBR; inhibit the phosphorylation of EGFR, possibly by interfering with the binding of EGF to EGFR XREF_BIBR; alter lipid organization in the plasma membrane (lipid rafts) and inhibit EGF binding to EGFR XREF_BIBR; and induce internalization of EGFR into endosomes XREF_BIBR."
sparser
"In MDD, cytokines from peripheral blood are transported to effector cells, which are then transported to the brain and interfere with the release of neurotransmitters.[ xref ]IL-1β, IL-6, and TNF are classic inflammatory factors that have been shown to promote the progression of MDD.[ xref ]Studies have shown that IL-1β, IL-6, and TNF are significantly elevated in the plasma and cerebrospinal fluid of MDD patients, and the content of these inflammatory factors is positively correlated with disease severity.[ xref ]Another study found that the expression level of TP53 was significantly increased in the plasma transcriptome of MDD patients.[ xref ]EGF can bind to EGFR, promoting cell growth, proliferation, and differentiation."
sparser
"EGF binds to the epidermal growth factor receptor (EGFR), which then dimerizes or forms ErbB-2, ErbB-3, or ErbB-4 homologs, increasing the intracellular activity of tyrosine kinase, activating effects such as cell proliferation, apoptosis and angiogenesis, embryonic growth, and tissue regeneration xref ."
sparser
"The presence of excess recombinant human EGF (rhEGF) protein inhibited binding of the EGF-bearing particles at 4°C ( xref ), showing that the particle interactions were dominated by the EGF-EGFR interaction rather than nonspecific associations between the capsid protein and the cell surface."
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"MSCs were cultured for two days on control or tEGF surfaces then placed on ice and incubated with 100 ng/ml of rhodamine labeled EGF for one hour, a protocol that would allow near-complete saturation of surface EGFR with labeled soluble EGF for adherent cells, based on ligand exchange kinetics for the EGF and EGFR complex on intact cells at 0degreesC."
sparser
"Although the EGFR
ectodomain was first crystallized in 1998, the detailed structure of the EGFR
ectodomain dimer bound to ligand EGF was not resolved until 2002 and provided
information on a completely novel and unexpected mode of activation for the
EGFR signaling pathway involving the dimerization process [ xref , xref – xref ]."
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"5 A canonical activator of ERK is the epidermal growth factor (EGF)/epidermal growth factor receptor (EGFR) interaction, in which EGF binding to EGFR leads to EGFR homo- and hetero-dimerization, recruitment of Grb2 and son of sevenless (SOS), activation of RAS, and downstream phosphorylation of RAF, MEK, and ultimately ERK."
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"We introduced the EGFP-EGFR-BTB BCL6 construct via lentiviral transduction into HEK293T cells and MCF10A mammary epithelial p53 −/− cells (referred to as MCF10A hereafter), whose proliferation is highly dependent on the EGF-EGFR signaling axis ( xref ), and confirmed stable expression and membrane localization of the EGFP-BTB BCL6 -coupled receptor in both cell lines ( xref A)."
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"Interestingly, the EGFconjugated DDS remarkably stabilized the interaction between EGF and EGFR, as shown by the stably low value of d (DI-DIII) in that complex.Hydrogen bonds between EGF and EGFRTo determine the binding strength between EGFR and the EGF-CS, SWCNT, and Drug complex, the percentage of H-bond occupations between the two proteins were calculated from the last 20 ns of MDSs and compared with the EGFR.EGF complex."
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"The three-dimensional structural prediction for EGF-ATTO655/EGFR complex (Figure xref ) showed that the interaction between EGFR and the EGF core is retained after ATTO655 conjugation, and the ATTO655-conjugated C-terminal region with high structural plasticity does not seem to interrupt either the binding of EGF to EGFR or the structure of EGFR."
sparser
"We therefore conclude that accelerated wound healing after inhibition of KCNN4 could be due to an activation of signaling pathways that are also activated by binding of EGF to its receptor EGFR, because wound closure cannot be further stimulated by additional application of EGF."
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"This demonstrates that reduction of intracellular ubiquitin resulting from preincubation of cells with lactacystin was not sufficient to inhibit EGF induced polyubiquitination of the EGFR and strongly supports the notion that proteasomal activity is essential for efficient transport of EGF bound EGFR to inner membranes of MVBs."
sparser
"Normally, epidermal growth factor (EGF) binding to EGFR homodimers stimulates receptor downregulation (via internalization), and this depends on recruitment of the E3 ubiquitin ligase, c-Cbl, to the phosphorylated receptors followed by c-Cbl-mediated EGFR ubiquitination and degradation [6]."
sparser
"EGF binds to its cognate receptor EGFR, leading to the phosphorylation of numerous tyrosine residues on its cytoplasmic domain [ xref ], which induce activation of downstream signal transduction components and regulate receptor trafficking, including internalization, recycling and degradation [ xref ]."
sparser
"Following EGF binding, EGFR undergoes conformational changes that result in receptor dimerization, autophosphorylation, kinase activation cascades and downstream signaling pathways responsible for regulating several cellular processes, including cell growth, differentiation, survival, and apoptosis [ xref ]."
sparser
"To block EGF-EGFR signaling, we used the Food and Drug Administration approved EGFR-targeted therapeutics (EGFR inhibitors, EGFRi) in NPC cells, including the monoclonal antibody cetuximab (Erbitux, ERB) and a small molecule afatinib (AFA, a tyrosine kinase inhibitor), both of which can directly bind to EGFR and block the EGFR pathway."
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"From the structural and energetic analysis, it can be stated that when EGF binds to EGFR in the tethered form, the interactions between EGF and the binding pocket domains I (mainly) and III will begin, and this then narrows the binding pocket and finally expands the EGFR structure by pulling domain II out from its interaction with domain IV (Ferguson et al., 2003)."
sparser
"EGFR is a transmembrane receptor that has intrinsic tyrosine kinase activity and has several specific ligands, such as the epidermal growth factor that binds to EGFR and initiates multiple signaling pathways essential for different cell functions. xref , xref Mutations of the EGFR genes may result in persistent activation of the tyrosine kinase related to EGFR in tumor cells, and may thus promote tumor proliferation, cell survival, and other cancer-related properties. xref , xref , xref TKI binds to the tyrosine kinase domain to inhibit the protein kinase activity of EGFR, and the EGFR mutation may be the most important predictor of responsiveness to TKI. xref , xref , xref , xref , xref In recent years, determination of EGFR gene status has played an extremely important role in TKI selection for advanced lung cancer treatment."
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"Thus, activation of a GPCR results in an immediate matrix metalloproteinase (MMP)-catalysed release from the cell surface of an EGF-family EGFR agonist [heparin-binding EGF, or transforming growth factor-alpha (TGF-α)], that in turn activates receptor tyrosine kinase (RTK) signal pathways that are quite distinct from those activated by the GPCRs on their own [46-48]."
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"Thus, activation of a GPCR results in an immediate matrix metalloproteinase (MMP)-catalysed release from the cell surface of an EGF-family EGFR agonist [heparin-binding EGF, or transforming growth factor-alpha (TGF-α)], that in turn activates receptor tyrosine kinase (RTK) signal pathways that are quite distinct from those activated by the GPCRs on their own [46-48]."
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"SPR analysis confirmed a high-affinity interaction between EGF and EGFR (26.1 nM, Supplementary Figure S5), with Trichoharzin significantly inhibiting this interaction in a concentration-dependent manner, reducing the binding affinity of EGF to EGFR to 191, 372, and 1740 nM at concentrations of 125, 250, and 500 μM, respectively (Figures 4E–G)."
sparser
"This bimodal interaction between EGF-EGFR signaling and TIMP-1 expression on the one hand, and TIMP-1 mediated stimulation of cell invasion, specifically on KRAS -mutated cells, on the other hand, suggested that the predictive value of TIMP-1 we observed is the outcome of two additive effects; first that TIMP-1 expression is under control of EGFR-signaling, independently of the RAS/MAPK-axis (Figures xref and xref ), and secondly that TIMP-1 potentiates an aggressive behavior in KRAS mutated cells but not KRAS wt cells (Figure xref )."
sparser
"Upon EGF binding to EGFR, the endocytic pathway is activated to downregulate EGFR expression through degradation or recycling. [ xref ] Antibodies direct against Le y have been characterized to have inhibitory effects on ErbB1 (EGFR) and ErbB2 signaling pathways through affecting the intracellular routing of the ErbB receptors, but not by abrogating EGF binding to receptors. [ xref ] Here, we demonstrated that the amount of EGFR expression in response to EGF was reduced in the absence of Le y modification."
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"The different mechanisms that have been proposed for the inhibition of EGFR by EGCG include 1) interfering with the binding of EGF to EGFR and inhibiting EGFR tyrosine kinase activity [XREF_BIBR], 2) altering lipid organization in the plasma membrane (lipid rafts) and inhibiting EGF binding to EGFR [XREF_BIBR], and 3) inducing EGFR internalization without activation [XREF_BIBR]."
sparser
"Instead, binding of EGF to the EGFR was confined to other membrane populations, and correlation of ligand interaction with the laterobasal membranes (LBM) was nearly perfect (p less than 0.001) across a special equilibrium gradient enriched in brush border and LBM but devoid of intracellular membranes."
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"We have taken advantage of the well characterized trafficking of the EGF and EGFR complex, the dependence of EGF receptor endocytosis on ligand binding, and previously developed cell-free endosome fusion assays, to develop a novel approach for measuring fusion of EGF-EGFR-containing compartments."
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"The family includes four receptors : ErbB-1 (EGFR), which binds EGF, transforming growth factor alpha (TGFalpha), the heparin binding EGF like growth factor (HB-EGF), amphiregulin (AR), betacellulin (BTC), epiregulin (EPR) and epigen, ErbB-2 (also called HER2), which has no known ligand, and two neuregulin (NRG) receptors, ErbB-3 and ErbB-4."
sparser
"In view of these often conflicting results we have performed detailed analytical ultracentrifugation, fluorescence polarisation and surface plasmon resonance studies of the EGF-sEGFR interaction using a soluble receptor preparation generated and purified without the use of detergents and denaturants."
sparser
"Other glycosylation sites such as N151, N328, and N603 on EGFR, and the choice of ligand, may impact the how ligand binding domain acts to stabilize EGFR-EGF binding. xref , xref Relative to wild-type EGFR, unglycosylated EGFR N603 mutants demonstrated increased propensity to dimerize without ligand, but were deficient at increasing cell survival in the absence of stimulatory ligand. xref EGF has higher affinity binding for EGFR than AREG, and as expected stimulation with EGF led to larger increases in proliferation than AREG. xref , xref ( xref – xref )."
sparser
"In the ligand-dependent mechanism, the stimulation of GPCRs via selective agonists triggers the membrane-bound matrix metalloproteases (MMPs)-mediated proteolytic cleavage of a pro-ligand, generating a cleaved ligand EGF that binds to EGFR and induces signal transduction [ xref , xref , xref ]."
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"To illustrate, Palma et al. designed and synthesized a multi-ligand functionalized, nanoscale particle containing spatially controlled A20FMDV2, an integrin alphaVbeta6 binding motif, and epidermal growth factor (EGF), a protein that binds the epidermal growth factor receptor (EGFR) which is a tyrosine kinase that cooperates closely with integrins XREF_BIBR."
sparser
"While xref and xref were among the first to show the preferential retention of ErbB2-containing heterodimers on the plasma membrane, recent experimental studies also support this hypothesis. xref showed that ErbB2 inhibits internalization of EGF bound to ErbB1 by driving heterodimerization. xref reported that internalization defective ErbB1 mutants commonly found in ErbB1-kinase-inhibitor-responsive non-small cell lung cancers display sustained signaling in response to EGF. xref showed that 184A1 HMECs with high ErbB2 expression had more sustained EGF-induced ERK activity compared to ERK responses from the same cell line with low ErbB2 expression."
sparser
"According to combined_SCORE numerical ranking, the top ten targets of connection strength ( xref ) are: AKT1:NOS3; CCNA2:CDKN1A; CCND1:CDKN1A; CCND1:ESR1; CDKN1A:PCNA; EGF:ERBB2; EGF:EGFR; ESR1:JUN; F3:F7; HIF1A:MDM2; Through the analysis of the obtained data files, we find 88 nodes, and 1468 edges as well as, the average node degree is 33.4; Average local clustering coefficient is 0.73; expected edge number is 388; PPI enrichment P value is less than 1.0 e-16. lastly Through Cytoscape3.7.2() software, six Hub bases are screened out according to drgee values, which are AKT1, IL6, VEGFA, CASP3, JUN and MMP9 ( xref )."
sparser
"When the upstream and downstream processes were correlated, certain relationships were observed for ES-treated HDFs, such as HGF with fibroblast proliferation and protein synthesis ( xref ), or the EGF–EGFR axis with fibroblast proliferation ( xref ), highlighting the presence of both growth factors in ES versus L-PRP."
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"In RTCs, binding of EGF to EGFR stimulates activities of ERK, phospholipase C (PLC), and SphK, resulting in increased intracellular levels of S1P, while the EGF and EGFR mediated Ca 2+ mobilization, which may regulate apoptosis, requires activation of PLC and SphK in HEK293 cells [XREF_BIBR]."
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"The EGFR protein binds the epidermal growth factor (EGF) and plays an important role in regulating cellular growth and function (Traish and Wotiz, 1987; St-Arnaud et al, 1988; Nishi et al, 1996; Itoh et al, 1998; Migliaccio et al, 2006; Bonaccorsi et al, 2004, 2007; Leotoing et al, 2007)."
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"Considering that TNBC and HER2 enriched breast carcinoma cells are highly dependent on the activation of EGFR and HER2, we performed bioluminescence resonance energy transfer (BRET) experiments to determine whether melittin interfered with the binding of EGF to EGFR, leading to the observed suppressed growth factor receptor phosphorylation."
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"The dual-ligand-displaying AaLS/TRAIL/EGFRAfb exhibited a dramatically enhanced cytotoxicity on TRAIL-resistant and EGFR-overexpressing A431 cancer cells in vitro, effectively disrupting the EGF-mediated EGFR survival signaling pathway by blocking EGF/EGFR binding as well as strongly activating both the extrinsic and intrinsic apoptotic pathways synergistically."
sparser
"Inhibition of VEGF–VEFR pathway can indirectly block the conduction of EGF–EGFR signaling pathway, thus achieving the effect of inhibiting cell proliferation. xref , xref The intersection of the downstream signaling pathways of VEGF–VEGR2 and EGF–EGFR were shown in Figure xref ."
sparser
"For the EGFR·EGF-CS-SWCNT-Drug complex, the closer binding pocket (Figure 6(c)) and increased β-sheet formation at residues ~310 and α-helix formation at residues ~470 (Figure 4(c)) promoted the stronger interaction between EGFR and the EGF-conjugated DDS, as clearly seen in Figure 8(a) (red)."
sparser
"However, further examination of these data suggests that while consistent with each individual isotherm, the simple model of two independent binding sites that is generally applied to EGF binding to the EGF receptor is inconsistent with the changes in the apparent K(D)'s seen across varying cell densities."
sparser
"When compared to wild‐type EGFR, the number of colonies formed by CYF10 EGFR mutant in the presence of EGF was significantly reduced, confirming the critical role of C‐terminal phosphorylation in the oncogenic activity of wild‐type EGFR (Fig. xref c and Supporting Information, Fig. S1)."
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"To examine whether recycling of EGF bound EGFR is regulated by pY374-PKCdelta, we generated BT-549 cells with doxycycline (dox)-inducible myc tagged PKCdelta (WT-PKCdelta-myc) or dox inducible PKCdelta rendered nonphosphorylatable at residue 374 by mutation to phenylalanine at this site (designated Y374F-PKCdelta-myc)."
sparser
"In other words, the binding of EGF to the EGFR extracellular domain results in a structural change leading to assembly of the intracellular asymmetric kinase interface; this structural signal is transmitted through the formation of an antiparallel coiled coil within the JM segment to which the binding and fluorescence of ReAsH is linked."
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"Because of its ability to bind EGFR, nimotuzumab can competitively interfere with the binding of EGF to EGFR, resulting in the blockade of downstream signaling pathways, inhibiting tumor cell proliferation, promoting tumor cell apoptosis, and enhancing the efficacy of radio- and/or chemotherapy."
sparser
"In the normal condition, the network signaling is initiated by binding of epidermal growth factor (EGF) to EGFR, followed by the dimerization and subsequent mutual trans-phosphorylation on several tyrosine residues of EGFR; although EGFR family has other three members including ErbB2, ErbB3, and ErbB4 in addition to EGFR (ErbB1) which can form different dimmers (either homo- or hetero-dimers) xref , xref , just EGFR and EGFR-EGFR homo-dimers are considered in this model for simplification."
sparser
"The requirement for the WASH complex in segregation of stress-internalized EGFR along with pre-melanosomal factors away from ligand-stimulated EGFR contrasts with the unimpaired lysosomal degradation of EGF-bound EGFR and plasma membrane recycling of TfR in WASH knockouts xref ."
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"In this system, EGFR can be activated by both EGF and TGF-alpha, XREF_BIBR, XREF_BIBR leading to clustering and internalization of the EGF and EGFR complex into early endosomes or membrane compartments characterized by tubular vesicular morphology and a mild acidic pH. From early endosomes, EGF receptors can be either recycled back to the plasma membrane (recycling pathway) or into multivesicular bodies (MVBs) for degradation in lysosomes."
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"Despite the lack of evidence for a single‐ligated asymmetric vertebrate EGFR dimer that would account for the observed ligand binding heterogeneity, single‐ligated dimers were identified in cells by co‐transfecting ligand binding‐deficient and kinase activation‐deficient EGFR mutants, which rescue phosphorylation when they interact together. xref The notion that these single‐ligated vertebrate dimers might display asymmetry, like in the fly homologue, was inferred by judicious structural analysis that compared the so‐called ‘flush’ dimer structure, displayed by the solubilised, truncated vertebrate ectodomain dimer in the absence of D IV (Figure xref ), xref with the ‘staggered’ conformation found in the crystal structures of the full length solubilised ErbB4 ectodomain bound to two Neuregulin 1β molecules, and of the full length solubilised human EGFR ectodomain bound to two EGF molecules, where the ectodomain D IV has not been truncated xref (Figure xref )."
sparser
"Data in xref showed that pre-incubation of the MDA-MB-468 cells with free EGF for 1 h significantly inhibited the cellular uptake of the EGF-GemC18-NPs, but not the OVA-GemC18-NPs, by the MDA-MB-468 cells, demonstrating that the uptake of EGF-GemC18-NPs was mediated by the EGF-EGFR interaction."
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"These results demonstrated that mn-STESS promoted the expression of EGFR through self-powered ES to improve pharmacodynamics, thereby enhancing the binding of EGF to EGFR, promoting the phosphorylation of EGFR, and accelerating cell migration and proliferation by activating the EGFR signaling pathway."
sparser
"The binding of EGF to EGFR leads to receptor dimerization, autophosphorylation and the activation of several downstream signaling pathways, such as the MAPK pathway and the PI3K/Akt pathway, which play roles in cell proliferation, motility, and survival [ xref ]; these pathways have also been shown to contribute to the abnormal growth of several types of human cancers [ xref ]."
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"Epidermal growth factor and transforming growth factor-alpha ligands bind and activate the EGFR receptor, followed by internalization of homodimerized or heterodimerized (EGFR binding HER-2 or ERBB3) receptors, leading to autophosphorylation of the intracellular tyrosine kinase domain and activation of several downstream pro oncogenic signaling pathways [XREF_BIBR]."
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"Amivantamab binds to the extracellular domains of EGFR and cMet and blocks the binding of the ligand EGF to EGFR and the binding of the ligand HGF to its receptor cMet; it also induces degradation of both receptors in vivo, extending its effects to Ligand-independent receptor-driven diseases are included (99), and can bind to immune effector cells through ADCC to eliminate antigen-expressing tumor cells (100)."
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"The EGF (epidermal growth factor)-like domain I within the extracellular domain of EpCAM (EpEX) binds to EGFR (epidermal growth factor receptor), activating AKT and MAPK (mitogen-activated protein kinase) signaling pathways, and inhibiting the function of forkhead transcription factor O3a (FOXO3a) and stabilizing PD-L1 protein, respectively."
sparser
"Research conducted by Jiang and his team, as well as Dong and his colleagues, has shown that intravitreal injections of antibodies against amphiregulin (another member of the EGF family), EGF, and EGF receptor are associated with dose-related and time-dependent decreases in negative lens-induced axial elongation in young guinea pigs and that intravitreally applied amphiregulin or EGF itself leads to an increase in axial elongation ( xref )."
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"While binding of EGF to EGFR induces autophosphorylation at tyrosine sites in the C-terminal non catalytic domain of the receptor that act as docking sites for various signaling molecules, Src transactivation of EGFR is characterized by phosphorylation at a unique Y845 site located in the kinase domain of EGFR that leads to activation of alternate signaling molecules [XREF_BIBR - XREF_BIBR]."
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"EGF selectively binds to EGFR and triggers the receptor to form a dimer that activates RAS which can transmit signals from the activated transmembrane receptor EGFR to effectors in the MAPK and PI3K/AKT signaling pathways in the cytoplasm, regulating cell survival and proliferation (43)."
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"In this respect, the biochemical events activated by androgens may be the increase in EGF and EGFR production, binding of EGF to its receptor, activation of tyrosine kinase activity with consequent cellular replication, internalization of the complex EGF and EGFR and receptor degradation in lysosomes."
sparser
"To investigate the possibility that higher EGF loading might cause steric effects on EGF-EGFR binding, and also to further interpret the observation that targeted 111 In-EGF-Au NP with the highest EGF loading shows the greatest internalization and radiotoxicity, a concept of footprint (k) (Hill et al. xref ) was introduced for modeling ( xref )."
sparser
"To compare the effect of gefitinib with an anti-EGFR antibody, NHEK were treated with cetuximab, an anti-EGFR humanized chimeric mouse monoclonal antibody, which competitively inhibits receptor binding of EGF and other EGFR ligands ( xref ). xref demonstrates that cetuximab was able to completely block [p]EGFR and [p]MAPK in primary human keratinocytes."
sparser
"As 111 In-EGF-Au NP generated using a mixing ratio of 160 showed greater internalization and radiotoxicity compared to 111 In-EGF-Au NP at lower mixing ratios, we assume that the gap between adjacent EGF molecules on Au NP is large enough to avoid steric effects on EGF-EGFR binding."
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"These results indicate that efficient membrane trafficking of the EGF and pEGFR complex from early endosomes to late endosomes occurs in PC9 cells, and also suggest that ligand induced EGFR signaling might operate in the early endosomes and late endosomes via the endocytic pathway."
sparser
"Activation of EGFR, in turn, activates its downstream kinases, such as AKT and ERK, thereby promoting cancer cell proliferation, invasion, and apoptosis resistance. xref , xref The binding of EGF to EGFR not only activates signals downstream of EGFR but also stimulates the rapid internalization of EGFR."
sparser
"Dimeric EGFR binding to two molecules of EGF is characterized by high-affinity and low-affinity events, which are proposed to represent an initial high-affinity binding event that favors an asymmetric dimeric structure in which the second subunit is sterically prevented from binding ligand [ xref ]."
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"We have previously reported that the EGF and EGFR complex associated with the plasma membrane is efficiently endocytosed and translocated to LIMPII positive late endosomes and lysosomes at 15 min after EGF stimulation in PC9 cells [XREF_BIBR]; therefore, our present data showing the efficient trafficking of pEGFR from the plasma membrane via early endosomes to late endosomes within 15 min of EGF stimulation is consistent with that reported previously."
sparser
"In case of EGFR, stimulation via TGFα and EGF leads to comparable rates of endocytosis, but EGF/EGFR-containing early endosomes more frequently fuse with lysosomes than those carrying TGFα/EGFR complexes, possibly due to a more stable interaction between EGF and EGFR under acidifying conditions [ xref , xref ]."
sparser
"Necitumumab inhibited the interaction of EGF and EGFR with a concentration that inhibits binding by 50 % of approximately 0.9 nM (0.13 mg/L) and demonstrated antitumor activity during in vivo experiments associated with trough plasma concentrations of approximately 40 mg/L. This work describes the population pharmacokinetics of necitumumab in cancer patients when administered with or without concomitant chemotherapy and evaluates patient characteristics that may guide dosing."
sparser
"In cells, the deletion of the leucine zipper caused a decrease in both the tyrosine phosphorylation of Cbl and its association with the epidermal growth factor receptor following stimulation with epidermal growth factor, thus demonstrating a role for the leucine zipper in c-Cbl's signaling functions."
sparser
"This was consistent with the upregulation of the majority of genes in EGF-EGFR, and its downstream pathways (PI3K-Akt, Rho GTPase, RAP1, and regulation of actin cytoskeleton) in PC3 revealed by our single-cell RNA-seq (scRNA-seq) data on prostate cancer and its prohibition by tyrphostin (AG 1478), which resulted in suppression of migration and invasion (Horning et al., data not shown)."
reach
"By co-IP, we confirmed that EGF-related protein EFEMP2 could bind EGFR (Fig. 5a), and the phosphorylation pathway profiling array analysis showed that the downstream pathway of EFEMP2 might be the c-Jun pathway, we further examined whether EFEMP2-EGFR binding could activate the ERK1/2/c-Jun pathway or the JNK/c-Jun pathway."
reach
"We exploited in silico approaches : molecular dynamics simulation at variable pH and MM-GBSA free energy of binding calculation method to evaluate the effect of this change in microenvironmental pH. Through the present study it is reported that at pH 6.6 the EGFR binds to EGF with decreased free energy of binding as compared to pH 7.2."
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"Our results also suggest that the components of this signaling axis may be potential therapeutic targets for bladder cancer patients undergoing cisplatin chemotherapy.In EGFR signaling pathways, EGF binding to EGFR triggers homodimerization or heterodimerization of this receptor with other ErbB members as well as receptor phosphorylation and activation of downstream effectors, such as RAS-RAF-MEK-ERK-MAPK and PI3K-mTOR, thereby leading to cell proliferation [58]."
reach
"EGF binds and dimerizes EGFR, leading to receptor autophosphorylation on various tyrosine residues on the receptor’s C-terminal tail region (Gullick et al., 1985; Böni-Schnetzler and Pilch, 1987; Honegger et al., 1987; Yarden and Schlessinger, 1987; Koland and Cerione, 1988; Linggi and Carpenter, 2006)."
reach
"Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha) and amphiregulin (AREG) bind to EGFR; heparin binding EGF like growth factor (HB-EGF), beta-cellulin (BTC), and epiregulin (EPR) bind to both EGFR and HER4; neuregulin-1 (NRG-1) and NRG-2 bind both HER3 and HER4; and NRG-3 and NRG-4 bind to HER4."
reach
"A recent study reported that the induction of EGFR mediated carbon monoxide releasing molecule-2 (CORM-2) in human bronchial smooth muscle cells promotes HO-1 expression, whereas in glioblastoma, the phosphoinositide 3-kinase (PI3K) signaling pathway is activated through the binding of EGFR and EGF to induce HO-1 expression [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
| PMC
sparser
"We recently reported that epidermal growth factor (EGF), which is expressed by BM ECs, xref , xref promoted NHEJ repair in HSCs following chemotherapy or total body irradiation (TBI) stress and that EGF treatment promoted restoration of the self-renewal capacity of young HSCs following irradiation in a DNA-PKcs-dependent manner. xref Separately, RNA sequence analysis of BM hematopoietic cells from middle-aged mice suggested that a decline in EGF signaling was associated with hematopoietic aging. xref We hypothesized that activation of EGF-EGFR signaling might restore some functions of aged HSCs."
sparser
"As common in modeling, the names of introduced components were highly abbreviated: A species resulting from the binding of EGF and EGFR is named as Ra (stands for activated receptor), aggregation of two Ra species forming a species D (standing for dimer), a species resulting from phosphorylation of D called Dp (representing the phosphorylated state), aggregation of the Grb2 species with Dp resulted in the species named DpG, which would become DpGS when it is aggregated with the Shc protein, DpGSp when phosphorylated, and finally, DpGsp_Sos when the Sos protein is aggregated onto the compound."
sparser
"Our transplantation assays utilized whole BM cells from EGF-treated and EGFR-deficient mice, rather than purified HSCs, so our studies do not exclude the possibility that EGF-EGFR signaling regulates the repopulating capacity of aged HSCs indirectly via other BM cell populations or niche effects."
sparser
"When protein EGF ( ) is bound to its receptor EGFR phosphorylated on tyrosine ( ), the GRB2-associated-binding protein or phosphorylated on tyrosine is present ( ), the Ras guanyl-releasing protein 3 or protein phosphorylated on tyrosine is present, is present, the protein phosphorylated on tyrosine is present, and the inside of the membrane ( ) contains loaded with guanosine diphosphate , then switches its load to guanosine 5 ′ -triphosphate [ xref ]."
reach
"Through scientific collaboration with Sigma-Aldrich, we developed a 2x-SRC homology 2 (SH2) domain based EGFP biosensor system, in which SH2 from the adaptor molecule Grb2 binds to tyrosine phosphorylated EGFR with high affinity upon epidermal growth factor (EGF)-triggered EGFR dimerization and activation [4]."
sparser
"The binding of EGF to the EGF receptor (EGFR) on the cell membrane stimulates the phosphorylation of SHC, which complexes with the GEF son of sevenless (SOS) and growth factor receptor-bound protein 2 (GRB2) to promote the binding of GEFs to KRAS, causing KRAS to exist in the activated GTP-bound state xref ."
reach
"EGFR is present in the plasma membrane in an autoinhibited state but once bound by epidermal growth factor (EGF) undergoes dimerization and autophosphorylation that triggers the activation of several downstream signaling cascades, including the PI3K–AKT–mTOR and MAPK/ERK pathways."
sparser
"In cells with physiological receptor expression levels, EGF binding to EGFR also triggers endocytosis through a clathrin-dependent pathway, whereas in EGFR overexpressing cells clathrin-independent pathways have been observed especially in the presence of high EGF concentrations. xref Importantly, the activated EGFR remains dimerized with the phosphorylated tyrosine kinase domain exposed in the cytoplasm after internalization into early endosomes. xref – xref In this fashion, the receptor continues to signal during intracellular trafficking until it is dephosphorylated by a protein tyrosine phosphatase xref , xref , the ligand is removed from the endosome, xref or the phosphorylated EGFR (pEGFR) containing endosome is encapsulated in a multivesicular body. xref The accompanying removal of the phosphorylated receptor tail from the cytoplasm renders the phosphorylated EGFR inaccessible and results in signal termination."
sparser
"EGFR frequently accumulates and is concomitantly mutated in a variety of cancers. xref Besides the classical degradation pathway that relies on EGF induction, EGF-independent proteasomal degradation plays a major regulatory role in maintaining EGFR protein homeostasis. xref , xref The EGF–EGFR complex is internalized into the cell and passes through early endosomes, late endosomes, and multivesicular bodies (MVBs) before reaching the lysosome, where it is degraded, thereby attenuating the EGFR-mediated signal. xref , xref Endosomal sorting complexes required for transport (ESCRT) are involved in this process, sorting the ubiquitinated receptor at the MVB to facilitate lysosomal degradation. xref The main function of the ESCRT system is to promote the degradation of ubiquitin-labeled membrane proteins, xref and it is also involved in cell division, virus germination, cellular autophagy, and fungal pH sensing. xref ESCRT consists of multiple protein complexes, most of which have been structurally resolved."
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"Since the EGFR also binds with several other ligands as well as EGF, the present study was designed to investigate whether PKG II inhibited transforming growth factor-alpha (TGF-alpha), betacellulin (BTC) and epiregulin (EPR) induced phosphorylation and activation of the EGFR and consequent MAPK and ERK mediated signaling."
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"The activation of this G protein increases the cAMP, and thus the epidermal growth factor receptor (EGFR) can bind to the epidermal growth factor (EGF), which initializes a signaling chain which will activate mitogen activated protein kinase (MAPK), and phosphatidyl-inositol 3 kinase (PIP3K) [113]."
sparser
"Several mechanisms have been proposed for the inhibition of EGFR by EGCG: (a) interfering with the binding of EGF to EGFR and inhibiting EGFR tyrosine kinase activity [ xref ]; (b) altering lipid organization in the plasma membrane (lipid rafts) and inhibiting EGF binding to EGFR [ xref ]; and (c) inducing EGFR internalization without activation [ xref ]."
sparser
"CNTF binds the CNTF receptor (CNTFR), ephrins bind to the Eph tyrosine kinase receptors, EGF binds to the EGF receptor (EGFR) or receptor homologs, GDNF binds predominantly GFRα1 in complex with the RET receptor, neuregulins bind the ErbB family of receptors, PGRN binds TNF receptors as well as the sortilin receptor, and lastly, TGF-β isoforms binds to the TGF-β type I, II, and III receptors (TβRI, TβRII, and TβRIII) ( xref ; xref ; xref ; xref ; xref ; xref ; xref ; xref )."
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"The binding of EGF to EGFR leads to receptor dimerization, autophosphorylation and the activation of several downstream signaling pathways, such as the MAPK pathway and the PI3K and Akt pathway, which play roles in cell proliferation, motility, and survival [XREF_BIBR]; these pathways have also been shown to contribute to the abnormal growth of several types of human cancers [XREF_BIBR]."
sparser
"Administration of purified soluble TM inhibited cell proliferation and invasion in murine melanoma. xref Furthermore, recombinant TM suppressed tumor growth by inhibiting thrombin‐induced activation of protease activate receptor‐1 (PAR1) and nuclear factor kappa B (NF‐κB) activation in pancreatic cancer cells. xref Kuo et al reported that the lectin‐like domain recognized and adhered the Lewis‐Y antigen of the EGF receptor (EGFR) on the surface of the cancer cell and subsequently inhibited the binding of EGF to EGFR and suppressed cell proliferation. xref On the contrary, our study showed no correlation between tumor size and differentiation and TM expression."
sparser
"Both theoretical and experimental works (Burgess et al., 2003; Dawson et al., 2005; Ferguson et al., 2003) have shown a high binding affinity of EGF towards the EGFR, while a kinetic study of the EGF-EGFR interaction suggested that EGF can bind with either an inactive expanded EGFR dimer or a tethered EGFR monomer before inducing the EGFR dimerization process (Björkelund, Gedda, Malmqvist, & Andersson, 2013; Lemmon, 2009)."
sparser
"The binding of EGF to the extracellular domain of EGFR induces dimerization of the receptor and the activation of its intrinsic tyrosine kinase activity, leading to receptor autophosphorylation and the phosphorylation of tyrosine residues in various downstream signaling molecules, including ERK1/2, AKT, STAT3, and PKC [ xref ]."
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"Also, since physiologically and pathologically EGF binding to EGFR leads to several downstream signaling cascades to promote cell proliferation and survival, targeting EGFR overexpressing cancer cells with EGF decorated nanocarriers may potentially trigger signaling processes that amplify cancer growth, thus offsetting the therapeutic effects of the nanocarrier delivered payload."
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"EGF binds to the epidermal growth factor receptor (EGFR), which then dimerizes or forms ErbB-2, ErbB-3, or ErbB-4 homologs, increasing the intracellular activity of tyrosine kinase, activating effects such as cell proliferation, apoptosis and angiogenesis, embryonic growth, and tissue regeneration ."
sparser
"Hyperglycemia can also promote epithelial-mesenchymal transition and proliferation of PDAC cells, via hydrogen peroxide ( xref ), epidermal growth factor and epidermal growth factor receptor (EGF-EGFR) pathway ( xref ) and transforming growth factor beta (TGF-β) signaling pathways ( xref )."