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"The three-dimensional structural prediction for EGF, ATTO655, and EGFR complex 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
"Domains of this type, also called cysteine-rich microdomains (size up to 40 aa residues), are often involved in protein–protein interactions, an example is a well-known EGF–EGFR interaction [ xref ], and are also considered as therapeutic scaffolds with a very stable central core [ xref ]."
sparser
"Yanagida and colleagues performed smFRET to study the interactions between EGF and EGF receptor (EGFR) in living cells using TIRF microscopy ( xref ). xref Since EGF binding to EGFR leads to receptor dimerization, a mixture of Cy3-labled EGF and Cy5-labled EGF were added to EGFR expressing cells."
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"Based on the> 20-fold reduced potencies of lapatinib for the L858R and Delta746-750 tEGFRs compared to EGF bound WT tEGFR, we hypothesize now that the kinase active conformation of EGF bound WT EGFR may be nearly isoenergetic with the kinase inactive state of EGF bound WT EGFR and largely present in the donor kinase."
sparser
"Concerning the high serum concentration of sEGFR in COPD-BS compared to COPD-TS, it is important to point out its possible relevance in the context of the LC, and the COPD phenotypes, because one of the main characteristics in COPD-BS is chronic mucus hypersecretion, which is closely associated with EGF-EGFR activity at the level of the airways. xref xref – xref sEGFR overexpressing in the epithelium of the airways in COPD-TS, and has been associated with the development of LC due to changes in its gene regulation; but very important due to its mutations associated with the activation of cell transformation, which are the second most common oncogenic driver event in ADC and NSCLC. xref "
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"Taken together, these results demonstrate that HIP1R is necessary for the ligand induced early endocytosis of EGFR.It is known that the binding of EGF to the surface EGFR triggers the dimerization and autophosphorylation of EGFR, and then induces the cellular internalization of EGFR (Iwashita and Kobayashi, 1992; Heldin, 1995; Lemmon and Schlessinger, 2010)."
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"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]."
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"XREF_BIBR, XREF_BIBR We discovered that the binding of epidermal growth factor (EGF) to the WT EGFR extracellular domain promotes formation of a distinct antiparallel coiled coil 15 within the intracellular JM, whereas the binding of transforming growth factor-alpha (TGF-alpha) is communicated through the formation of a coiled coil - a rotational isomer - whose helical interface is ' inside-out ' compared with the JM interface formed in the presence of EGF (XREF_FIG)."
sparser
"In contrast, upon bFGF stimulation, the increased EGFR expression which was observed in our experiments, may be induced by a cross-talk between EGFR and FGFR signaling pathways which often overlap. xref FGFR activation upon bFGF binding may stimulate similar signaling transducers as binding of EGF to EGFR."
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"For the co-localization of EGFR and EEA1, although EEA1-colocalized EGFR clusters were increased after ligand stimulation, such increment was also largely abolished in HIP1R knockdown group (Figures 4C,E), indicating that HIP1R mediates the internalization of EGFR after EGF stimulation.To investigate HIP1R’s role in EGFR internalization more directly, we examined the internalized Alexa labeled EGFR ligand EGF (Alexa -EGF) to visualize the internalization of EGF-EGFR complex."
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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
"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."
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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."
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"Similarly, Lidke and colleagues demonstrated that Qdot conjugated EGF binds and activates the EGF receptor erbB1, being rapidly internalized into endosomes that exhibit active trafficking and extensive fusion in A431 cells (epidermal carcinoma) and CHO cells (chinese hamster ovary) 46."
sparser
"A plausible explanation for decreased EGF-induced receptor dimerisation and tyrosine phosphorylation could be that addition of AnxA2 (D1/274.5) antibody blocked AnxA2 function, resulting in the inhibition of EGF binding to EGFR and/or recruitment of other proteins which are critical for EGFR function."
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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
"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."
sparser
"In parallel, we found that dynamin inhibition using Dynasore did not affect either HD ( xref ), ITGA6 uptake ( xref ), or ITGB4 turnover, as measured by FRAP ( xref ), although it prevented the uptake of epidermal growth factor–bound (EGF-bound) epidermal growth factor receptor (EGFR) (Supplemental Figure S7), showing that HaCaT cells are sensitive to it."
sparser
"SINET is the most common malignancy of the small intestine. xref Epigenetic changes in GAD1 expression facilitates cancer metastasis by altering glutamate metabolism in the microenvironment of metastatic brain cancer. xref Conversely, among the downregulated genes in our mRNA signature, FGF10 signaling was previously reported to play a role in the development of aggressiveness in pancreatic cancer cells through interactions with FGFR2 (FGF receptor 2); xref the abolishment of PGC-1α was associated with the resistance of pancreatic cancer stem cells against the anti-diabetic drug metformin; xref EGF, as a part of the tumorigenic EGF-EGFR system in PAAD, could induce translocation of RhoA from the cytosol to the membrane fraction and cause cell rounding in human pancreatic cancer cells, and such a process could be reversed by high-mobility group-coenzyme A (HMG-CoA) reductase inhibitor fluvastatin. xref Noticeably, the EGFR inhibitor erlotinib offers a potential therapeutic tool in PAAD treatment."
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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
"These AFM results provide novel information about the binding between EGF and EGFR in KYSE-150 cells at single molecule level, and also enhance our understanding about how oridonin inhibit EGFR signaling events by inhibiting EGF-EGFR binding, which is very important for the pharmacological studies of oridonin against EGFR in living cancer cells."
sparser
"The facilitated uptake of the pSIN-β plasmid in the EGF-conjugated liposomes by the EGFR-over-expressing tumor cells was mediated by the EGF-EGFR interaction, because pre-incubation of the tumor cells with free EGF significantly inhibited the uptake of the plasmid ( xref ), whereas pre-incubation with free EGF did not significantly affect the uptake of the pSIN-β plasmid complexed with the EGF-free PEG-liposomes ( xref )."
sparser
"Studies have reported that heparin-binding EGF (HB-EGF) can bind to EGFR when mediated by sulfated HSPG, thereby promoting sustained phosphorylation of EGFR on Tyr1068 and Tyr992 residues and activating the downstream AKT and ERK signaling pathways to promote cancer cell proliferation and migration [ xref ]."
sparser
"Under the conditions of the FA experiments, isolated sEGFR (without zipper or Fc fusion) remains monomeric; the FA assay contains just 60 nM EGF, so the maximum concentration of EGF-bound sEGFR is also limited to 60 nM – which is over 20-fold lower than the K D for dimerization of the EGF/sEGFR complex ( xref ; xref )."
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."
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"The possibility that ectodomains of EGFR inhibit EGFRs signaling by sequestering their ligands comes from the observation by Garrett et al that a truncated EGFR with only 3 of the 4 extracellular subdomains binds EGF and TGF-alpha with at least ten-fold higher affinity than the full-length extracellular domain of EGFR rendering them unavailable for binding to and activation of receptors."
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"Within this epidermal growth factor receptor ligand family, EGF, transforming growth factor-alpha (TGFalpha), and amphiregulin bind HER1, neuregulins-1 and -2 bind to either HER3 or HER4, heparin binding EGF (HB-EGF), betacellulin (BTC), and epiregulin bind to either HER1 or HER4, and neuregulins-3 and -4 are specific for HER4 [XREF_BIBR - XREF_BIBR]."
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 ]."
sparser
"The marine natural product naamidine A (NA) was isolated in 1987 from the marine sponge Leucetta chagosensis ( xref ). xref During the initial biological evaluation of NA, it was reported that the natural product exhibited submicromolar inhibition of epidermal growth factor (EGF)-stimulated DNA synthesis, a response that was not observed with other mitogenic stimuli. xref Although NA inhibited EGF-mediated signaling in A-431 cells, it was demonstrated that this effect occurred independently of EGF-EGFR binding."
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"Furthermore, transient disruption of the Golgi complex by brefeldin A (BFA) treatment did not alter EGF binding or EGFR trafficking per se (Figure S7E–G), suggesting that the LRRK2-mediated endolysosomal trafficking deficits are neither mimicked by RAB29 inactivation nor dependent on Golgi integrity."
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"To understand whether the increase in autophagic markers observed in MPS VI cells is due to the deficient ability of lysosomes to recycle metabolites, we compared the Epidermal Growth Factor (EGF)/EGF Receptor (EGFR) turnover in MPS VI and NR fibroblasts based on the knowledge that binding of EGF to EGFR induces ubiquitination, rapid internalization and degradation of both ligand and receptor via the lysosomal pathway [XREF_BIBR, XREF_BIBR]."
sparser
"Using this technique, we have studied the process of early signal transduction of epidermal growth factor (EGF) in single molecules: binding of EGF to its receptor (EGFR) on the cell surface, dimerization of EGFR induced by binding of EGF, fluctuation of the structure of EGFR clusters, activation of EGFR through tyrosine phosphorylations on its cytoplasmic domain, and recognition of activated EGFR by a cytoplasmic adaptor protein, Grb2."
sparser
"Furthermore, the kinase activity can be significantly stabilized by reconstituting purified EGF-bound EGFR dimers in phospholipid nanodiscs or vesicles, suggesting that the environment around the hydrophobic transmembrane and amphipathic juxtamembrane domains is important for stabilizing the tyrosine kinase activity in vitro ."
sparser
"The EGF‐like repeat domain interacts with the epidermal growth factor receptor, and the fibronectin III‐like repeat domain binds integrins to promote adhesion and mediates cell activation via toll‐like receptor 4, leading to sustained inflammation. xref The unfavourable effects of TNC on ventricular remodelling in DCM might result from ongoing myocardial damage or inability to repair the failing heart because of sustained inflammation."
sparser
"Specifically, each EGFR monomer binds an EGF ligand, exposes its unique dimerization arm, and then forms an asymmetric dimer. xref Within this dimer, the C‐terminus of one EGFR containing multiple phosphorylation sites inserts into the kinase domain of another EGFR, an allosteric interaction that activates the receiving kinases and results in trans‐autophosphylation. xref In the absence of ligands, EGFR can also be activated by other receptors, such as G‐protein‐coupled receptors and cytokine receptors, and therefore can act as signal integrator. xref Subsequently, phosphorylated EGFR initiates myriad key signaling pathways, among which the most studied are MAPK/ERK, PI3K/Akt, SRC, PLCγ/PKC, and JAK/STAT."
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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
"The expression profiles of genes encoding kinases were distinctive for each of the three PA lineage: NR5A1-derived tumors showed upregulation of ETNK2 and PIK3C2G and alterations in MAPK, ErbB and RAS signaling, POU1F1-derived adenomas showed upregulation of PIP5K1B and NEK10 and alterations in phosphatidylinositol, insulin and phospholipase D signaling pathways and TBX19-derived adenomas showed upregulation of MERTK and STK17B and alterations in VEGFA-VEGFR, EGF-EGFR and Insulin signaling pathways."
sparser
"The model also suggests that panitumumab inhibits the interaction between EGFR and EGF in a similar way to cetuximab; EGF binds to domains I and III of EGFR.[ xref ]The interface between EGFR domain I and EGF overlaps the EGFR-antibody interface in the panitumumab model and cetuximab crystal structure."
sparser
"Furthermore, the kinase activity can be significantly stabilized by reconstituting purified EGF-bound EGFR dimers in phospholipid bilayer nanodiscs or vesicles, suggesting that the environment around the hydrophobic transmembrane and amphipathic juxtamembrane domains is important for stabilizing the tyrosine kinase activity in vitro ."
sparser
"Yeast cells coexpressing the cell-wall-anchored form of the human epidermal growth factor (EGF) and the human EGF receptor (EGFR) fused with a signal peptide at the N terminus facilitated the interaction of EGF with EGFR in an autocrine manner, followed by EGFR oligomerization and subsequent autophosphorylation."
sparser
"Interestingly, with EGFR relocalization, we found that clathrin was also relocalized to the EGF::EGFR micropattern ( xref ; see also xref for quantification), suggesting that the EGF micropattern traps EGFR in an intermediate state along the endocytic pathway, as expected if the micropattern activates the physiological signaling cascade downstream of EGFR activation but prevents EGFR endocytosis because of the strong link to the micropattern."
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"This may be because the intestinal mucosal surface was completely saturated with EGFR as when EGFR is fully bound to EGF, even if there is excess EGF, it cannot perform its biological functions due to the lack of corresponding receptors.Transcriptome sequencing can detect all the transcript information of tissue in different physiological states (39), providing a new technical means for examining the pathogenesis of NEC and the mechanism of EGF."
sparser
"To understand whether the increase in autophagic markers observed in MPS VI cells is due to the deficient ability of lysosomes to recycle metabolites, we compared the Epidermal Growth Factor (EGF)/EGF Receptor (EGFR) turnover in MPS VI and NR fibroblasts based on the knowledge that binding of EGF to EGFR induces ubiquitination, rapid internalization and degradation of both ligand and receptor via the lysosomal pathway [ xref , xref ]."
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"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."
sparser
"Epidermal growth factor (EGF) binds to the EGF receptor on external cell membrane and stimulates cell signalling, modulating the activity of enzymes involved in specific pathways including transcriptional regulators, small GTPases and kinases by stimulating phosphorylation events xref – xref ."
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"In contrast, they remained associated with EGFR in Tip30 -/- MECs (EGF-EGFR colocalization in wild type primary MECs : 11%; EGF-EGFR colocalization in Tip30 -/- primary MECs : 55%; n = 20, P = 0.004; XREF_FIG), indicating that Tip30 deletion causes the trapping of EGF and EGFR complex in endosomes and sustained endosomal EGFR signaling."
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"With respect to pre-EMT carcinoma cells, STAT3 is predominantly activated by the binding of EGF to EGFR (i.e., EGF dependent; XREF_FIG, left), and to a lesser extent, by the binding of FN to a complex comprised of alphavbeta3 integrin and EGFR (i.e., EGF independent; XREF_FIG, middle)."
sparser
"Apart the already cited sorafenib, regorafenib, and erlotinib, the drugs brivanib, gefitinib, lapatinib, imatinib, and apatinib were also introduced in clinical studies as anti-EGFR drugs, thus confirming the important role played by the pathway EGF-EGFR in the development of HCC."
sparser
"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/EGFR-loaded vesicles; (iii) newly formed endocytic vesicles loaded with EGF/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/EGFR."
sparser
"TGF-α is a member of the epidermal growth factor (EGF) family which binds to epidermal growth factor receptor and has been recently identified to be involved in osteoarthritis pathology, where its expression was found to be upregulated in osteoarthritic chondrocytes in a rat model of ACLT-induced osteoarthritis [ xref ]."
sparser
"We have attempted to derive a mathematical model for EGF binding to the EGFR and for ligand-induced receptor dimerization and activation that uses this structural information and can explain the characteristic concave-up curvilinear Scatchard plots seen when EGF binding to intact EGFR is studied in living cells."
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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 search for endocytic properties that may be exploited to predict responsiveness to gefitinib, Nishimura et al. [ xref ] used confocal immunofluorescence microscopy to compare the endolysosomal distribution of fluorescent EGF-EGFR complexes in gefitinib-sensitive NSCLC PC9 cells expressing the D746–750 EGFR mutant and gefitinib-resistant QG56 cells expressing wtEGFR."
sparser
"The K D value for EGF binding to dimeric sEGFR wild-type was essentially the same (within 2-fold) as that for sEGFR Y251A/R285S ( xref and xref ), arguing that the favorable Gibbs Free Energy (ΔG) of liganded sEGFR dimerization (−5.5 to −8 kcal/mol) does not contribute significantly (< 0.4 kcal/mol) to enhanced ligand-binding."
sparser
"This affinity is four orders of magnitude stronger than that of the original antibody 7D12–sEGFR interaction ( K D 2.19 × 10 −7 M) ( xref ), three orders of magnitude stronger than that of the EGF–sEGFR interaction ( K D 6.0 × 10 −8 M) ( xref ), and two orders of magnitude stronger than that of the cetuximab–sEGFR interaction [ K D ranges from 2.3 × 10 −9 M ( xref ) to 8.4 × 10 −9 M] ( xref )."
sparser
"In the meantime though, while one study reported that in U87 glioma cells EGF induced tyrosine phosphorylation of nuclear β-catenin and increased β-catenin transcription activity, little is known about the intranuclear mechanisms via which β-catenin activity is regulated by EGF–EGFR signaling."
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 ]."
sparser
"A monoclonal antibody to the EGF receptor (13A9) has been identified which has only small effects on the binding of EGF to the EGF receptor, but which has very large effects on the binding of TGF alpha to the EGF receptor; 5 micrograms/mL antibody has been shown to totally block 0.87 microM TGF alpha from binding to purified EGF receptor and to lower both the high- and low-affinity binding constants of TGF alpha binding to EGF receptor on A431 cells by about 10-fold."
sparser
"Therefore, the principles and the reagents used to devise this homogeneous assay were adapted to various models representative of molecular and cellular processes and were chosen from the signaling pathways involved in cellular communication and expression: epidermal growth factor (EGF) receptor-ligand interaction, EGF receptor kinase activity, Jun/Fos protein-protein interaction, and DNA hybridization."
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."
sparser
"Finally, it is suggested that HCMV binds epidermal growth factor receptor (EGFR) as part of the internalization of the virus, which also causes the mobilization of intracellular calcium, a response that is known to occur with native ligand binding of EGF to EGFR (Wang et al., xref )."
sparser
"Mucin-1 plays important roles in cancer development and metastasis by inhibiting the anti-tumor immune response [ xref ], promoting the growth of cancer cells by binding to EGFR in an epidermal growth factor-dependent manner [ xref ], preventing cell death by inhibition of p53-mediated apoptosis and promotion of p53-mediated cell cycle arrest [ xref ], and promoting cancer metastasis [ xref - xref ]."
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
"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 ]."
sparser
"For example, G6-31 is an improved anti-VEGF antibody derived from a phage display library with better binding affinity and enhanced therapeutic efficacy in animal models than Avastin. xref To improve tumor penetration, a single-domain antibody of 15 kDa against EGFR from a llama has been recently developed (termed anti-EGFRVHH). xref , xref This llama nanobody was nonimmunogenic in mice and was proven to block binding of EGF to EGFR, thereby inhibiting EGFR signaling and showing the specific tumor targeting. xref , xref Anti-EGFRVHH is used for molecular imaging and therapeutic applications. xref , xref FAP (also known as seprase), a highly conserved protein, is richly expressed particularly in the stroma of aggressive cancers. xref The high-level expression of FAP is correlated with cancer progression. xref To date, no specific molecular inhibitor of FAP has been developed. xref , xref M036, a species-cross-reactive FAP-specific single-chain antibody (scAb), was isolated by sequential phage display and was shown to bind FAP on stromal cells of different human carcinomas and the murine host stroma in human tumor xenografts. xref The therapeutic potential of M036 has not yet been evaluated."
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 ]."
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"The unitary association processes mirrored the EGF and ErbB1 interactions in HeLa cells [Teramura Y, et al. (2006) EMBO J 25:4215-4222], suggesting that the predimerization of the receptors, followed by intermediate formation (between the first and second ligand binding events to a receptor dimer), accelerated the formation of doubly liganded signaling dimers of the receptor molecules."
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"The (125) I-EGF - EGFR interaction on cell line U343 is sensitive to starvation while as on SKBR3 it is insensitive to gefitinib and starvation.The intriguing pattern of the binding characteristics proves that the cellular context is important when deciphering how EGF interacts with EGFR."
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"In some cases, ligand binding can influence the fate of a receptor : for example, internalized EGF-R bound to EGF is targeted to lysosomes for degradation, whereas the alternative ligand TGF-alpha is released from the receptor in acidic EEs, resulting in efficient EGF-R recycling to the plasma membrane."
sparser
"The heat map ( xref C and xref ) indicates 18 interactions enriched in FGFRL1-KD xenografts, including growth and differentiation factors with their respective ligands, including the pairs SEMA4F–NRP2, EFNB3–EPHB3, FGF2–FGFR3 or GPC4, EGF–EGFR, VEGFC–KDR or FLT4, and INHBA–ACVR1B3."
sparser
"Attempts were made to sort EGFR-positive MSCs but high EGFR levels were not maintained in culture and the populations reverted to variable EGFR expression (data not shown), which may be related to an autocrine EGF-EGFR negative feedback response and ligand-induced internalisation of the EGFR [ xref ]."
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"Our results suggest there is no significant difference between the dissociation constants of EGFR homodimers with 1) double-ligand EGF occupancy, 2) asymmetric dimers of one ligand-bound monomer and one 425 scFv bound receptor, and 3) double 425 scFV ligated dimers.We concluded that gefitinib pretreatment yielded a more stable EGF-bound EGFR dimer, whereas the scFv inhibitor did not exert any measurable effect."
sparser
"The binding of EGF receptor to EGF causes receptor dimerization and induces phosphorylation of tyrosine residues in tyrosine kinase domain located in the intracellular tail of receptor, which recruits many signaling proteins, such as PI3-K, PLC- γ , PLD, Shc, and Grb2 proteins, phosphotyrosine phosphatase 1, and others, and transduces hormonal signal to different intracellular effector proteins and systems [ xref ]."
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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]."
sparser
"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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"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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"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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"The N glycosylation of the glycosyl group next to the EGF binding site in EGFR could cause its noncovalent interactions with the EGFR extracellular domain, stabilizing the EGF binding site, leading to a stronger interaction between EGF and EGFR; N glycosylation also helps maintain the binding of the EGFR dimer and plays a special role in the binding of antibodies and the extracellular domain of EGFR XREF_BIBR."
sparser
"These kinases were chosen due to their known importance to schistosome biology: a) epidermal growth factor receptor (EGFR, SER), which binds human EGF and induces signalling in the worm [ xref , xref ]; b) PKCβ, which plays an important role in schistosome larval development and possibly regulates pairing and egg release of adults [ xref , xref ]; c) extracellular signal-regulated kinase 2 (ERK2), which together with ERK1, regulates the maintenance of the ovaries and thus egg production [ xref ]; d) Akt, which plays an important role in glucose uptake in adult worms [ xref ]; and e) PKA, which is important in schistosome motor activity and survival [ xref , xref ]."
sparser
"When epidermal growth factor ligands bind to the EGFR , they activate a signalling pathway cascade, mediated by downstream effectors of the mitogen-activated protein kinase ( MAPK ) pathway and other pathways including the phosphoinositide-3-kinase ( PIK3CA )/ AKT signalling pathway."
sparser
"Binding of the epidermal growth factor (EGF) ligand to EGFR induces homo- or hetrodimerization of the receptor and activation of the kinase domain, ultimately leading to intracellular signaling events, including activation of protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinase (MAPK)."
sparser
"These downstream pathways such as the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway [ xref ], the phosphoinositide 3-kinase (PI3K) pathway [ xref ], and the phospholipase C (PLC) pathway [ xref ], are activated when epidermal growth factor (EGF) binds to the extracellular domain of EGFR."
sparser
"Therefore we determined EGF expression for each of the four systems, and then treated with an inhibitor in order to block interactions between the macrophage-derived EGF and the EGF receptor (EGFR) known to be upregulated on carcinoma cells, including MDA-MB 231 [ xref , xref ]."
sparser
"Because there are clear differences in the trafficking routes of EGF-bound EGFR compared with unliganded receptor ( xref ; xref ), we next asked whether PTPN14 also regulates EGF-induced trafficking of EGFR and whether this is dependent on its substrate, pY374-PKCδ (PKCδ that is phosphorylated on Y374; xref )."
sparser
"In contrast to other RTKs, which are activated in the presence of a bivalent ligand that induces dimerization by interacting with two receptors (in a 1:2 ratio of ligand to receptor), one EGF molecule interacts with a single EGF receptor; thus, an activated receptor is constituted by a 2:2 ratio of ligand to receptor ( xref ; xref )."
sparser
"One difference in how these studies were conducted is temperature: those which reported AP-2 siRNA to have an effect on EGFR entry were performed at 37° C; ( xref ), while in the two which claimed no role for AP-2 in EGFR endocytosis EGF binding was performed at 4° C ( xref ; xref )."
sparser
"The key role of the EGFR in negative prognosis in
various malignancies
resulted in the development of numerous anti-EGFR agents, and several
of them have been advanced to the clinic. xref Moreover, several synthetic small molecules and monoclonal antibodies
targeting the EGFR family tyrosine kinases in breast cancer are in
different phases of trials. xref Cetuximab
is an immunoglobulin G1 chimeric mouse–human monoclonal antibody,
which targets the extracellular domain of the EGFR and has been approved
for combinational therapy with irinotecan in the treatment of EGFR-expressing
metastatic colorectal cancer (CRC) refractory patients. xref Similarly, Panitumumab, a humanized immunoglobulin
G2 monoclonal antibody, acts by blocking the interaction between the
EGF and EGFR and has been approved for the treatment of EGFR-expressing
metastatic CRC patients. xref Moreover, several
heterocyclic small molecules have been approved for the treatment
of various cancers including breast cancer."
"The ErbB family of four receptor tyrosine kinases occupies a central role in a wide variety of biological processes from neuronal development to breast cancer. New information continues to expand their biologic significance and to unravel the molecular mechanisms that underlie the signaling capacity of these receptors. Here, we review several aspects of ErbB receptor physiology for which new and significant information is available."
reach
"The binding of EGF receptor to EGF causes receptor dimerization and induces phosphorylation of tyrosine residues in tyrosine kinase domain located in the intracellular tail of receptor, which recruits many signaling proteins, such as PI3-K, PLC-gamma, PLD, Shc, and Grb2 proteins, phosphotyrosine phosphatase 1, and others, and transduces hormonal signal to different intracellular effector proteins and systems [XREF_BIBR]."
sparser
"Since monoclonal antibody specific for the EGF receptor abolished both EGF binding to its receptor and tyrosine phosphorylation of the c-erbB-2 gene product, we have concluded that activation of EGF receptor tyrosine kinase activity upon EGF binding leads to the phosphorylation of the c-erbB-2 gene product on its tyrosine residues."
reach
"Use of phospho specific antibodies against pY-1068 or pY-1173 of EGFR (rapidly phosphorylated after EGF binds the EGFR) on western blots of cell lysates from the three MTLn3 lines at various times after EGF stimulation (XREF_FIG) revealed no statistically significant differences in the kinetics of EGFR auto-phosphorylation (XREF_FIG)."
sparser
"Additionally, AFM was also applied to investigate the effect of Trastuzumab, as well as Pertuzumab, on HER2-modulated EGF-EGFR interactions, which demonstrated that EGF bound to EGFR more stably in the cells co-expressing EGFR and HER2, and the binding enhancement in the presence of HER2 was inhibited by either Trastuzumab or Pertuzumab [ xref ]."
sparser
"In this study, we identified the clathrin uncoating ATPase Hsc70 as an Hrs UIM-interacting ubiquitinated protein and provided evidence that Hsc70 is an essential component of the machinery that regulates Hrs-mediated endosome-to-lysosome trafficking of internalized EGF-EGFR complexes."
reach
"The epidermal growth factor receptor (EGFR) is regarded as a prototypical cargo of the MVB and ESCRT pathway and following stimulation by epidermal growth factor (EGF) EGFR and EGF complexes are internalized, sorted into MVBs, and degraded by lysosomes or recycled back to the cell membrane."
sparser
"So, for example, it is commonly assumed that the functional form of the hGH/hGH-R complex on cells involves a termolecular complex in which a single hGH molecule is bound to two molecules of hGH-R, and similarly that the functional complex for EGF-R is a 2:2 complex in which two EGF-bound EGF-R molecules are associated back-to-back."
sparser
"The distribution of the top enriched pathways for the up-regulated genes indicated enrichment in inflammatory response and T-cell receptor signaling, while pathway analysis performed on the down-regulated genes revealed enrichment in mitogen-activated protein kinase, TGF-β, senescence, FAK, adipogenesis, androgen receptor, and EGF–EGFR signaling pathways in SVF from ED patient."
sparser
"Single-molecule tracking reveals that the predominant mechanism of dimerization involves the formation of a cell-surface complex of one EGF molecule and an EGFR dimer, followed by the direct arrest of a second EGF molecule, indicating that the EGFR dimers were probably preformed before the binding of the second EGF molecule."
sparser
"Our results demonstrated that oridonin could dramatically inhibit EGF-EGFR interactions through decreasing the unbinding force, decrease the binding probability, decreasing the energy barrier width, increasing the dissociation off rate constant and decreasing the activation energy in ROS dependent way."
sparser
"Overall, our data suggests that upon EGF stimulation, EGF-EGFR complexes are rapidly transported to enlarged pre-existing EE vesicles in MDAMB231 cells, where EGF-mediated signaling remains activated for prolonged periods, when compared to MCF10A. Importantly, this data is consistent with previous results suggesting that endosomal size can affect EGFR signaling, cell differentiation and cancer progression ( xref , xref – xref )."
reach
"2D NS-EM class averages revealed heart-shaped particles, resembling those previously seen for the EGF-bound extracellular EGFR dimer, providing first structural characterization of the HER2/HER3 heterodimers, and showing, for the first time, that HER3 adopts an extended conformation upon ligand binding (discussed in detail in (Diwanji et al., 2021))."
reach
"Two notable examples are discussed here : (1) In canonical receptor tyrosine kinase (RTK) pathways, binding of the epidermal growth factor (EGF) to its receptor EGFR and ErbB1 at the cell surface triggers receptor dimerization and cross phosphorylation of the EGFR intracellular kinase domains; phosphorylated domains then recruit and activate effectors such as the small GTPase Ras and the lipid kinase PI3K."
sparser
"The total interaction energy(E tot ) was − 64.76, − 63.0, − 69.5, and − 66.7 kcal/mol for: (I) EGF docking with the extracellular domain of EGFR; (II) EGF docking with the extracellular domain of EGFR-urea complex; (III) EGF-urea complex docking with the extracellular domain of EGFR; and (IV) EGF-urea complex docking with the extracellular domain of EGFR-urea complex, respectively (Fig. xref f)."
reach
"Stimulatory effects of EGF on cellular process were generated by binding into its specific receptor (EGFR) and interaction between EGF and EGFR induced intra-cellular signal transduction, including mitogen activated protein kinase (MAPK) and extracellular signal regulated kinase (ERK)."
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 ]."
reach
"Notably, incubation of purified Flag-MIF with purified GST-OGA, which resulted in the removal of MIF O GlcNAcylation (XREF_FIG), reduced the binding of MIF to EGFR (XREF_FIG) and failed to block the binding of EGF to EGFR (XREF_FIG) and EGF induced EGFR phosphorylation (XREF_FIG)."
sparser
"Since both cetuximab and panitumumab have negatively charged surfaces and cetuximab lacks a central cavity it is harder to predict which single point mutations could allow binding of cetuximab but prevent panitumumab binding while maintaining a functional EGFR that can bind to EGF."
sparser
"Surfactant protein D binds directly to high mannose-type N-glycans in EGFR and the interaction blocks the binding of epidermal growth factor (EGF) to EGFR, suppressing EGF signaling and inhibiting the proliferation and migration of two human lung adenocarcinoma epithelial cell lines, indicating that lung cancer cells are regulated by SP-D via autocrine mechanisms (158, 178)."
sparser
"Based on (1) cigarette smoking reduces the junctional barrier integrity of the airway epithelium, partially mediated by the EGF-EGFR signaling [ xref , xref ], to allow the particles/proteins to go across the barrier junctions of the airway epithelium, (2) our observation that BMP4 is expressed abundantly in the airway epithelium of smokers, we hypothesized that up-regulated BMP4 passes through the damaged barrier junctions of the airway epithelium, and interacts with BC to switch the normal BC self-renewal and differentiation toward smoking relevant abnormal airway epithelium."
sparser
"Hanna et al. demonstrated that heterotypic TNTs between breast tumor cells and macrophages were responsible for induction of an invasive tumor cell morphology in dependence on signaling via the EGF-EGFR (epidermal growth factor-epidermal growth factor receptor) pathway [ xref ]."
sparser
"Cetuximab is a recombinant human/mouse chimeric monoclonal antibody that binds to the extracellular domain of human EGFR, competitively inhibits the binding of EGF and other ligands to EGFR, blocks receptor phosphorylation and activation of receptor-associated kinases, and consequently inhibits the signaling cascade xref ."
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."
sparser
"These results led the investigators to propose that activation of the receptor occurs when EGF binds to two EGF-R monomers and induces them to dimerize, bringing the receptor cytoplasmic domains together and thereby promoting trans-phosphorylation of the receptor kinase domains to initiate signaling."
sparser
"Functional activation of EGFR is due to the formation of either EGFR-EGFR homodimers or of heterodimers with one of the other three members of the EGFR family of growth factor receptors (HER-2, HER-3, and HER-4) following binding of an EGFR-selective ligand, such as EGF, transforming growth factor alfa (TGF-alfa), or amphiregulin."
reach
"Previous results [Faulkner-O'Brien et al. (1991) Biochemistry 30,8976-8985] indicated that the reaction of [15N,2 H16] BSSDP with wild-type mEGF did not yield a product useful for ST-EPR studies of the EGF and EGF receptor complex because the major product, in which [15N,2 H16] BSSDP was attached only at the amino terminus of mEGF, lacked rigid motional coupling of the spin probe to the protein, and the more tightly coupled bidentate product was unstable."
sparser
"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."
reach
"Specifically, Dabertrand et al demonstrated that the diminished myogenic response in TgNotch3 R169C mice is caused by an increase in the number of voltage gated potassium (K V) channels in smooth muscle cells, and further showed that this defect could be rescued by promoting epidermal growth factor receptor (EGFR)-mediated K V channel endocytosis using the EGFR agonist heparin binding epidermal growth factor (HB-EGF)."