IndraLab
Statements
EGFR phosphorylates itself. 1000 / 1875
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26
1849
sparser
"A similar observation was also made for the EGFR:PDGFRβ (Saito et al., xref ) and ErbB2:NTRK1 (Tagliabue et al., xref ) heterodimers, in which EGFR family member auto-phosphorylation occurred following ligand activation of the interacting receptor, even in the presence of their respective kinase domain inhibitor."
sparser
"Based on these results, we conclude that TPA-induced AP-1 activation requires the basal level-EGFR protein, but not EGFR tyrosine kinase and EGFR autophosphorylation at tyrosine(1173), whereas both EGFR tyrosine kinase and EGFR autophosphorylation at Y(1173) play a critical role in EGF-induced AP-1 activation."
sparser
"Structural and biochemical studies have shown that oncogenic EGFR mutants, unlike wild‐type EGFR, can undergo constitutive receptor dimerization and consequent autophosphorylaton of the receptor in the absence of EGF or alternatively though activating mutations within the EGFR kinase domain that induce an active conformation not dependent on ligand‐induced asymmetric dimerization. xref , xref , xref Furthermore, accumulating data suggest that the downstream signaling pathways activated by oncogenic mutant EGFR differ from those activated by ligand stimulated wild‐type EGFR. xref , xref , xref Notably, C‐terminal deletion EGFR mutants, lacking some or all of the autophosphorylation sites that have been identified in GBM and lung adenocarcinoma, are able to induce cellular transformation. xref , xref , xref These observations have raised the question whether autophosphorylation of oncogenic mutant EGFR, which is a consequence of constitutive receptor dimerization, is required for oncogenic activation and induction of cellular transformation by cancer‐derived EGFR mutants."
sparser
"In addition, MNNG strongly blocks the autophosphorylation of EGFR in response to its ligand, we speculate it might be due to the altered conformation of EGFR by MNNG alkylation, or the binding of some unknown suppressive molecules to EGFR, which could lead to the down-regulation of EGFR pathway."
sparser
"Secondary ALK mutations are major causes of resistance to inhibitors and were found in 20%–35% of tumors resistant to crizotinib. xref , xref , xref ALK gene amplification was also found in 8.3% of crizotinib‐resistant tumors, and other bypass signal activations such as KRAS mutation, EGFR mutation, amplification of KIT , and increased autophosphorylation of EGFR were found in tumors resistant to crizotinib. xref , xref , xref Secondary ALK mutations were found more frequently in tumors resistant to second‐generation ALK inhibitors than in those resistant to first‐generation inhibitors. xref Two studies recently reported the mechanism of lorlatinib resistance. xref , xref One study investigated the mechanism of lorlatinib resistance in longitudinal tumor samples from five patients with ALK ‐positive lung cancer."
sparser
"If palmitoylation of the EGF receptor were responsible for the observed decrease in autophosphorylation of the CC-EGF receptor, then blocking palmitoylation of this receptor should reverse the decline in autophosphorylation observed in this mutant but should have no effect on the kinase activity of the wild type or SS-EGF receptors."
sparser
"Of these enriched proteins, 12 have previously validated physical interactions with EGFR ( xref , green datapoints), xref including CD44 , a transmembrane glycoprotein known to regulate EGFR autophosphorylation. xref Additionally, one of the most enriched proteins, AXL , is a known substrate of EGFR phosphorylation. xref EPHA2 and EPHB2 , also receptor protein-tyrosine kinases, were highly enriched in our dataset and are known to modulate vesicular trafficking of EGFR . xref Together, these data validate the accuracy of µMap-Red as a proximity labeling platform for profiling spatial connections in signaling pathways."
sparser
"In contrast, blocking EGF internalization by deletion of dynamin, a mediator of endocytic fission of coated pits, or knockdown of clathrin enhances EGFR autophosphorylation and sustains Akt stimulation, a downstream molecule in EGF signaling (Sousa et al ., xref ), indicating that EGF signaling is terminated by endocytosis."
sparser
"In vitro studies indicate that the quinazoline fragments, after conjugation to the cyano group (L1, L2) or to the pyrazolyl containing chelator (L5H), as well as the corresponding Re complexes (7, 8, 10) inhibit significantly the EGFR autophosphorylation and also inhibit A431 cell growth."
sparser
"Among the various RTKs, we focused on EGFR for two reasons: 1) it is a prototype RTK, and 2) EGFR autophosphorylation is best characterized, with in-depth understanding of the function of each autophosphorylation site and the signaling intermediates/adaptors that they recruit ( xref ; xref ; xref ; xref ; xref )."
sparser
"Similarly, in the JO22903 trial of erlotinib in Japanese patients, PFS was longer in patients with Del19 mutations than those with L858R mutations. xref The difference in outcomes between Del19 and L858R requires further research; however, preclinical studies suggest that Del19 and L858R mutations have different biological properties, with patterns of EGFR amplification and EGFR autophosphorylation differing between cell lines containing these mutations. xref , xref "
sparser
"A comparative study in the same cell line on the effects of the 2,2'-diselenobis(1H-indole) derived from (R)-tryptophan vs its disulfur congener on growth factor mediated tyrosine phosphorylation showed that this compound significantly inhibited EGFr and PDGFr (in response to its ligand) autophosphorylation with complete suppression at 25 and 5 microM, respectively."
sparser
"Multiple major signal transduction pathways are initiated by EGFR autophosphorylation, including the Ras-MAPK signaling cascade, Src, and the signal transducers and activators of transcription (STAT) pathways, which are widely used by growth signals to induce gene transcription and promote diverse cell responses."
sparser
"We demonstrated the specificity of these responses to stimulation by EGF by treating the cells with (i) the Src inhibitor PP2, which uncoupled EGF from phosphorylating EGFR on Y845, but was without effect on EGFR autophosphorylation ( i.e., Y1116) and ERK1/2 activation; and (ii) the EGFR inhibitor AG1478 (AG), which prevented all three EGF-driven responses ( xref )."
sparser
"Gefitinib, a small‐molecule kinase inhibitor that directly competes with adenosine triphosphate (ATP) to bind to EGFR, can inhibit EGFR autophosphorylation and downstream signaling. [ xref , xref ] Although such inhibitors have been used with success in nonsmall cell lung cancer (NSCLC) treatment, clinical trials in breast cancer have shown poor results, even in combination with chemotherapy. [ xref , xref ] It has been reported that NSCLC‐resistant cells enhance EGFR levels due to dysregulated degradation following loss of binding to its E3 ubiquitin ligase Cbl. [ xref ] In addition, it has been hypothesized that mAb and TKI resistance are partly due to activation of alternative downstream pathways of EGFR."
sparser
"Because the substrates of Shp2 are for the most part unknown, we were additionally interested in examining the state of EGFR tyrosine phosphorylation following treatment with EGF in order to determine if the failure of Gab1 to bind p85, and potentially recruit Shp2, would influence levels of EGFR autophosphorylation."
sparser
"In particular, at significant lower concentrations than gefitinib (1), (2R,3R)-N-(4-(3-bromoanilino)quinazolin-6-yl)-3-(piperidin-1-ylmethyl)oxirane-2-carboxamide (6) inhibited EGFR autophosphorylation and downstream signaling pathways, suppressed proliferation, and induced apoptosis in gefitinib-resistant NSCLC H1975 cells, harboring the T790M mutation in EGFR."
sparser
"In addition, compared with compounds 6 and 10 , these two negative controls ( 27 and 28 ) displayed lower potency at inhibiting EGFR autophosphorylation (p-EGFR) and its downstream signaling (e.g., AKT phosphorylation (p-AKT)), suggesting that the pharmacological degradation of EGFR can enhance the inhibition of the downstream signaling."
sparser
"ERRFI1 is thought to inhibit the autophosphorylation of the EGFR family and the downstream signaling proteins, principally in the MAPK, AKT and JNK pathways, ultimately inhibiting DNA synthesis and cell proliferation (i.e., a potential further contributor to the slowing down of critical cellular functions)."
sparser
"In vitro studies have suggested that SOCS4 is involved in regulating epidermal growth factor (EGF) signaling xref , and indeed the SOCS4-SH2 domain binds with high affinity to a phosphopeptide corresponding to an EGF receptor (EGFR) autophosphorylation site (Tyr1092; 0.5 µM) xref ."
sparser
"To further characterize the mechanism of this antigrowth factor activity, which is accompanied by an increase of high-affinity EGF binding and a drastic decrease in EGF receptor autophosphorylation, we studied the effect of OH-Tam on protein tyrosine phosphatase (PTPase) activity with specific in vitro assays using two different substrates."
sparser
"The compound entered clinical trials in 1999, based on its favorable preclinical profile: potent inhibition of EGF-mediated signalling in cells, in vivo antitumor activity in several EGFR overexpressing xenograft tumor models in nude mice, long-lasting inhibition of EGF-stimulated EGFR autophosphorylation in tumor tissue, good oral bioavailability in animals, and no prohibitive in vitro and in vivo toxicity findings."
sparser
"Given that T. gondii MIC3/6-mediated EGFR autophosphorylation and invasion-dependent Y845 EGFR phosphorylation occur almost simultaneously, it is possible that changes in conformation in the kinase domain induced by ligand (MIC)-mediated EGFR activation may facilitate the ability of Src to phosphorylate Y845."
sparser
"Moreover, DCN is able to activate epidermal growth factor receptor (EGFR)‐mediated receptor auto-phosphorylation and downstream signaling pathways, such as the mitogen-activated protein kinase (MARK)1/3 pathway, to mobilize intracellular calcium, and activate other EGFR‐dependent pathways in tumor cells to suppress cell growth ( xref ; xref )."
sparser
"Again, this finding was supported by our confocal microscopy analysis, which showed that the cell-surface pool and most of the internalized, trafficking EGFR were bound to ERRFI-1, and by western blot, which showed that baseline EGFR autophosphorylation was lower in the mesenchymal background as compared to the epithelial background of UMUC3 cells and the expression of miR-200c facilitates the EGFR downstream signaling pathways towards MAPKinase modulation."
sparser
"It is worth commenting on the fact that 4-anilinoquinazolines are well established as an effective template for the design of inhibitors of epidermal growth factor receptor (EGFR) and other members of the ErbB kinase family. xref In fact, dichloro analog 9 has been reported to moderately inhibit EGFR autophosphorylation (IC 50 = 2.7 μM) in A431 cells. xref While this level of potency is markedly less than that observed toward mGlu 5 in our functional cell based assay, monitoring potential off-target activity against such kinases will be necessary in the further development of this series as mGlu 5 non-competitive antagonists."
sparser
"These data indicate that tyrosine 992 is critical for substrate phosphorylation and internalization only in the context of the truncated receptor, and that minor autophosphorylation sites, such as Y992, may act as compensatory regulatory sties in the absence of the major EGF receptor autophosphorylation sites."
sparser
"Several mechanisms of resistance have been described, the most common of which is a secondary resistance mutation located in the ALK tyrosine kinase domain, the L1196M mutation, which acts as a gatekeeper mutation analogous to the T790M mutation in EGFR mutant NSCLC. xref – xref Additional resistance mutations that have been described are the G1269A substitution in the ATP binding pocket and the G1202R and G1206Y mutations in the solvent-exposed region of the kinase domain. xref , xref In a series of 11 ALK -positive patients with acquired resistance to crizotinib, 2 patients, one with a resistance mutation, exhibited amplification of ALK . xref Indeed, EML4-ALK gene amplification was associated with the emergence of resistance in EML4-ALK NSCLC cell lines treated with increasing doses of crizotinib. xref In addition to secondary ALK mutations and ALK gene amplification, activation of other kinases, including increased autophosphorylation of EGFR and amplification of KIT , could contribute to maintenance of downstream signaling and diminish the efficacy of crizotinib. xref , xref Finally, KRAS mutations were identified in 2 out of 14 patients with acquired resistance to crizotinib in a study by Doebele et al, implicating KRAS mutations as a possible resistance mechanism. xref "
sparser
"Through the inhibition of EGFR-TK autophosphorylation, signal transduction is inhibited to down-regulate cancer cell proliferation. xref , xref Erlotinib induces expression of cell cycle inhibition protein p27 to arrest cancer cell cycle in G phase, possibly useful for patients with locally advanced-stage or metastasis non-small cell lung cancers."
sparser
"Temporal analysis of tyrosine phosphorylation by mass spectrometry (MS) applied to EGF-stimulated cells has revealed phosphorylations with rapid kinetics (i.e. reaching maxima within seconds to a few minutes), such as EGFR auto-phosphorylations, which are associated with signal transduction (e.g. ERK activation), and others that accumulate with relatively slower kinetics (i.e. reaching a maxima after 30 min) that are involved in receptor downregulation xref , xref – xref ."
sparser
"Also, in agreement with previous reports xref , xref , EGF stimulation of DUOX1-expressing H292 cells resulted in increased EGFR autophosphorylation as well sulfenylation (analyzed by labeling with DCP-Bio1 and analysis of avidin-purified proteins; Fig. xref ), both of which are transient and reversed over time xref (see also Fig. xref )."
sparser
"In vitro studies indicate that both the ligand and its Re complex inhibit the EGFR autophosphorylation (IC(50): 17+/-3.7 and 114+/-23 nM respectively) in intact A431 cells, bind the receptor in a reversible mode, and inhibit A431 cell growth (IC(50): 5.2+/-1.1 and 2.0+/-0.98 microM respectively)."
sparser
"The result showed that ibrutinib was most potent against EGFR (L858R/T790M) (IC 50 : 9 nM), moderately potent against EGFR (T790M) (IC 50 : 50 nM), however slightly less potent against wt EGFR (IC 50 : 96 nM). (Table xref and xref ) A similar activity trend was observed for WZ4002, CO-1686 and AZD9291. ( xref ) Mass spectrum study with EGFR(T790M) protein revealed that ibrutinib did inhibit EGFR kinase through formation of a covalent bond with Cys797 amino acid and further confirmed the inhibitory activity loss with PCI-R compound observed in Table xref . ( xref ) For auto-phosphorylation of EGFR Y1068 in intact cell lines, ibrutinib exhibited an EC 50 of 23–58 nM in EGFR primary mutant cell lines (PC-9, HCC827, and H3255) and relatively weaker potency in EGFR L858R/T790M mutant cells (H1975: EC 50 : 145 nM). (Table xref and xref ) Interestingly, in the wt EGFR-expressing A431 cell line, the auto-phosphorylation of EGFR Y1068 was significantly inhibited by ibrutinib (EC 50 : 49 nM), while WZ4002 (EC 50 : 1436 nM), CO1686 (EC 50 : > 3000 nM) and AZD9291(EC 50 : 818 nM) were much less potent."
sparser
"Nevertheless, a crucial growth and cell survival mechanism coapted in MPM is the hyperactive signaling initiated by RTK subfamilies, many of which are overexpressed in MPM. xref , xref , xref Asbestos fibers can induce pathologic RTK signaling by autophosphorylation of EGFR (overexpressed in most MPM) as well as autophosphorylation of MAPK, inducing the subsequent pathway cascade. xref Loss of common tumor suppressors associated with MPM contribute to sustained activation of such signaling: NF2 xref loss influences Ras, and PTEN xref loss dysregulates PI3K/Akt."
sparser
"From the results, we found that ISO competitively targeted EGFR with EGF and inhibited EGFR auto-phosphorylation, and then decreased the levels of p-Erk1/2, p-PI3 K, and p-AKT, and further induced down-regulation of p-FOXO1 and promoted FOXO1 nuclear translocation; and finally resulted in a significantly up-regulation of Bim/p21/27/Bax/cleaved Caspase-3/cleaved PARP-1 and a markedly down-regulation of Sp1/Bcl-2/XIAP/Cyclin D1."
sparser
"We compared autophosphorylation of wild-type EGFR with that of three variants with mutations in Domain IV (II/KK; VEN/ERR; TN/RR; see xref for the positions of the mutated residues). xref shows the phosphorylation levels for Tyr 992, the proximal site, and Tyr 1173, the distal site, for wild-type EGFR and the mutants at an intermediate level of expression in the FACS assay."
sparser
"NIH‐3T3 mouse fibroblast‐like cells exogenously expressing EGFR with the sensitive mutation showed higher levels of EGFR autophosphorylation and greater sensitivity to EGFR‐TKI compared to those expressing exogenous wild‐type EGFR . xref Therefore, we tested whether the enhancement of the antitumor effect of gefitinib by KU55933 is associated with the EGFR mutation."
sparser
"Hydrolysis of 1-[4-(m-tolylamino)-6-quinazolinyl]-3-methyltriazene (SMA41) gives rise to an intact TKI [6-amino-4-(3-methylanilino)quinazoline; SMA52] capable of inhibiting epidermal growth factor (EGF)-induced EGFR autophosphorylation and a DNA-targeting methyldiazonium species."
sparser
"As shown in Figure xref in H322 cells EGFR autophosphorylation was unaffected when cells were treated with gefitinib-conditioned medium collected from Calu-3 in the absence of α-NAP, in contrast when the inhibitor was present in the gefitinib-conditioned medium, EGFR autophosphorylation was completely inhibited."
sparser
"mAbs cetuximab (an anti-IgG1) and panitumumab (an anti-IgG2) act by binding to the extracellular domain site of the receptor, whereas erlotinib and gefitinib, two EGFR TKIs, compete with the binding site of ATP to the TK portion of the receptor, resulting in the inhibition of EGFR autophosphorylation."
sparser
"This agent in particular acts as a reversible tyrosine kinase inhibitor that competes with ATP to inhibit EGFR autophosphorylation and the subsequent stimulation of downstream cell processes. xref It is currently approved for the treatment of advanced, metastatic non-small cell lung cancer and pancreatic cancer in adults."
sparser
"The binding of EGF to its receptor represented one of the first events identified as being capable of inducing robust activation of STAT3. xref Indeed, the activation of STAT3 by EGF receptor (EGFR) requires Src to phosphorylate the catalytic domain of EGFR at Tyr845, as well as at two EGFR autophosphorylation sites located at Tyr1068 and Tyr1086, both of which serve as docking sites for STAT3. xref , xref Moreover, EGF simulation of carcinoma cells that express aberrantly high levels of EGFR is sufficient to induce EMT phenotypes. xref Along these lines, Lo and colleagues xref demonstrated that the ability of EGF to induce EMT programs was contingent upon the activation of STAT3 in human tumors that harbored genomic amplifications of EGFR."
sparser
"EGFR autophosphorylation takes place in the context of a full-length transmembrane receptor, where distal portions of the tail, as well as other parts of the kinase domain, might affect the docking of short peptide motifs at the active site and thereby the rates and levels of phosphorylation in cells."
sparser
"In vitro treatment of HRCC cells with PKI166 inhibited EGF-R autophosphorylation, which correlated with a decrease in expression of Bcl-xl protein and phosphorylation of signal transducers and activators of transcription, particularly signal transducers and activators of transcription 3."
sparser
"Surface plasmon resonance of a peptide mimicking the EGFR JMD revealed strong binding to phosphatidylinositol-4,5-bisphosphate (PIP 2 ), and in cellular studies downregulation of PIP 2 levels or neutralization of negatively charged amino acids in the membrane-proximal, charged cluster of the JMD abolished this interaction, which was accompanied by reduced EGF-induced EGFR autophosphorylation and signaling [ xref ]."
sparser
"In this study, we investigated the effects of the quinazoline ZD1839, a potent, selective EGFR-TKI, on the EGFR autophosphorylation and cellular proliferation of androgen-sensitive (ND1, LNCaP, and ALVA-31) and androgen-independent (PC3, DU145, and TSU-Pr1) human prostatic cancer cell lines and 20 primary cultures derived from human prostatic cancer tissue."
sparser
"We identified that the structural modification of compound 19 by attachment of a bulky group on pyrrole ring along with an electronegative group on quinazoline ring and a hydrogen-bond donor on methyl formate opens a new avenue towards the optimization of novel chemical entities to develop potent inhibitors for EGFR autophosphorylation."
sparser
"Two classes of EGFR inhibitors have been developed for cancer therapy: tyrosine kinase inhibitors (TKIs), which block EGFR autophosphorylation by competing with ATP binding, and anti-EGFR monoclonal antibodies (mABs), which compete with the ligand binding the extracellular domain of EGFR."
sparser
"The remission rates of radiotherapy and chemotherapy for the treatment of NSCLC disease were only 25%‐35% and 15%‐20% respectively. xref In recent years, the study of targeting the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) has become a hot spot in NSCLC treatment. xref , xref , xref , xref That is, by competitively binding extracellular ligand binding sites with ATP or other substrates, blocking EGFR tyrosine autophosphorylation and tyrosine kinase activation, leading to EGFR activation inhibition and downstream signal transduction disorder, ultimately inhibiting cell cycle progression, accelerating apoptosis, disrupting angiogenesis, invasion and metastasis. xref , xref Gefitinib is a commonly used EGFR‐TKI drug for NSCLC treatment."
sparser
"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 ) revealed no statistically significant differences in the kinetics of EGFR auto-phosphorylation ( xref )."
sparser
"For example, it has been proposed that the ganglioside
GM3 inhibits epidermal growth factor receptor (EGFR) autophosphorylation, xref and the activation of toll-like receptor 4 has
been reported to be inhibited by another two gangliosides (GM1 and
GD1A). xref These studies suggest that lipids
could affect ectodomain activity, perhaps by influencing the positioning
of the receptor in the membrane."
sparser
"The current study was designed to address the following mechanistic questions related to the clinical efficacy of gefitinib and erlotinib: ( xref ) Are differences in drug responsiveness observed in EGFR autophosphorylation patterns for individual tyrosines in 32D cells expressing WT and L858R forms of EGFR?; ( xref ) Are some downstream pathways more significant than others when comparing normal and oncogenic EGFR signaling?; and ( xref ) Can we identify key tyrosines in EGFR or downstream signaling molecules that may play prominent roles in determining drug sensitivity in the context of oncogenic EGFR signaling?"
sparser
"A representative
biological activity of GM3 is inhibition of epidermal
growth factor receptor (EGFR) autophosphorylation. xref Like native GM3, the C -linked GM3 analogues
( 4 and 6 – 8 ) clearly
inhibited EGFR autophosphorylation induced by EGF in the membrane
fraction prepared from A431 cells ()."
sparser
"HNE (0.1 µM) is reported in a human endothelial cell line to modify and induce autophosphorylation of the epidermal growth factor receptor (EGFR) which is associated with activation of intrinsic tyrosine kinase activity and implicated in cell proliferation/differentiation xref ."
sparser
"Their data and that of McLaughlin et al. [ xref ] showed that binding of calcium-phospho-CaM to a positively charged segment of the EGFR cytoplasmic domain separated the segment from the inner leaf of the plasma membrane, resulting in a conformational shift that allowed full autophosphorylation of EGFR."
| PMC
sparser
"In order to determine whether EGFR transactivation is required for CXCL12/CXCR4-mediated signaling in prostate fibroblasts, N1 cells were pre-treated with inhibitors that block CXCR4 activation (25 μM AMD3100, AMD); EGFR auto-phosphorylation (500 nM AG1478, AG), or TGFβRI activation (SB431542, SB)."
sparser
"Ba/F3 and PC‐9 cells expressing the EGFR in‐frame deletion within exon 19 (del ex19)/T790M/C797S triple‐mutant were sensitive to lamellarin 14 in a dose range similar to the effective dose for cells expressing EGFR del ex19 or del ex19/T790M. Lamellarin 14 decreased the autophosphorylation of EGFR and the downstream signaling in the triple‐mutant EGFR PC‐9 cells."
sparser
"In another study, four head-and-neck squamous cell carcinomas (HNSCCs), four cervical carcinomas, five non small cell lung cancers (NSCLCs), four colon carcinomas, the epidermoid carcinoma cell line A431, and the breast adenocarcinoma MCF-7 were treated with lipophilic lovastatin, which inhibited EGF-induced EGFR autophosphorylation and its downstream signaling cascades ( xref )."
sparser
"Exposure to cigarette smoke downregulates DKK1 and leads to activation of Wnt signalling. xref Cigarette smoke also downregulates microRNA-487b, which mediates cell cycle arrest and senescence in lung cancer cells, by targeting WNT5A, a non-conical Wnt ligand, and components PRC1 and PRC2 of the polycomb repressive complex. xref Furthermore, cigarette smoke activates the arachidonic acid cascade through β1-adrenergic receptors and β2-adrenergic receptors and the subsequent expression of COX2, 5-lipoxygenase, VEGF, and matrix metalloproteinases. xref – xref Additionally, cigarette smoke modulates canonical ligand-dependent EGFR signalling through reactive oxygen species induced autocrine shedding of the EGFR ligands HBEGF, AREG, and TGF-α. xref – xref Oxidative stress due to cigarette smoke induces non-canonical EGFR autophosphorylation at Src-dependent phos phorylation sites leading to recruitment of Src to EGFR, which triggers the Ras/Raf/MEK/ERK and PI3K/AKT signalling cascades and contributes to tyrosine-kinase inhibitor resistance in tyrosine-kinase inhibitor sensitive lung cancer cells. xref – xref "
sparser
"Neutralization of positively charged amino acids abolished EGFR/PIP 2 interaction in the context of this peptide and down-regulated epidermal growth factor (EGF)-induced EGFR autophosphorylation and EGF-induced EGFR signaling to ion channels in the context of the full-length receptor."
sparser
"In particular, upon exposure of rat mesothelial cells to crocidolite, the most intensively investigated fiber for its effects on mammalian cells, autophosphorylation of epidermal growth factor receptor (EGFR) and activation of extracellular-regulated kinases 1 and 2 (Erk1/2), with consequent AP-1 transcriptional activity have been reported [ xref , xref ]."
sparser
"Evaluation of the efficacy of these compounds indicated that they were able to abolish EGFR autophosphorylation and postreceptor events such as activation of mitogen-activated protein kinases and the phosphatidylinositol 3'-kinase pathways as well as increases in Bcl-x(L) mRNA and protein levels."
sparser
"Here, we investigate, in vivo and in vitro, three aspects of the interaction between APs and EGF-R: firstly, we ask whether EGF-R at the plasma membrane distinguishes between AP-1 and AP-2; secondly, we ask which part of the receptor's cytoplasmic tail is responsible for binding; finally, we ask whether autophosphorylation by EGF-R is essential for the interaction."
sparser
"These gefitinib tumor concentrations are considerably higher than those reportedly required in vitro to achieve complete inhibition of epidermal growth factor receptor autophosphorylation in both epidermal growth factor receptor mutant (0.2 micromol/L) and wild-type cells (2 micromol/L)."
sparser
"This compound inhibits EGF receptor autophosphorylation in cells with an IC50 in the low nanomolar range and does not block PDGF or FGF receptor kinase until concentrations are greater than 10 microM. [1] Human epidermoid carcinoma A431 cells were grown in the presence of PD 153035 and were passed weekly until cells grew in the presence of 1 microM inhibitor."
sparser
"Here we show that overexpression of a scaffold protein, tumor necrosis factor receptor (TNF-R)-associated factor 4 (TRAF4), promotes EGF-induced autophosphorylation of EGFR (activation) and downstream signaling, whereas TRAF4 deficiency attenuates EGFR activation and EGF-driven cell proliferation."
sparser
"It has also been shown that cyclin D1 expression which mediates proliferation of tumor cells is a result of EGFR autophosphorylation leading to its complexing with PI3K and subsequent activation of ERK and AKT, and that under stress conditions such as growth factor deprivation, tumor cell dormancy is promoted as a result of decreased active AKT and cyclin D1 levels due to failed ERK-PI3K complex formation [ xref ]."
sparser
"EGFR autophosphorylation sites including Tyr 1092 , Tyr 1172 and Tyr 1197 , as well as canonical downstream phosphosites (for example, SHC1 Tyr 427 ; GAB1 Tyr 627 ; CBL Tyr 700 ) were similarly decreased upon osimertinib treatment in both NAF and CAF CM ( xref and xref , xref and xref ) suggesting that the sensitization to osimertinib was not due to changes in direct EGFR signaling."
sparser
"Most of the compounds exhibited good potency against EGFR wild type (EGFR wt) and EGFR T790M/L858R. Among these, the half-maximal inhibitory concentration (IC50) values of 17 compounds against EGFR wt were less than 0.020μM, and those of 12 compounds were less than 0.010μM. The IC50 values of 10 compounds against EGFR T790M/L858R were less than 0.005μM. Compounds 8l, 9n, 9o, 9q and 9v almost completely blocked the phosphorylation of EGFR in the A431 cell line at 1μM. Compounds 8l, 9n, 9o, 9q and 9v blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (1μM), and compound 8l was confirmed to be an irreversible inhibitor through the dilution method."
sparser
"Furthermore, the association of Src with Shc, Grb2 and the EGFR after angiotensin II stimulation [ xref ], together with previously described Src-mediated phosphorylation of tyrosine residues Y845 and Y1101 of the EGFR [ xref , xref ], suggest an additional means of receptor activation utilized by GPCRs that is distinct from EGFR autophosphorylation."
sparser
"In cellular assays, SU11925 exhibited similar potency against EGFR and HER-2, inhibiting EGF-stimulated EGFR autophosphorylation in A431 (human epidermoid carcinoma) cells with an IC(50) of 30 nM and HER-2 phosphorylation in SK-OV-3TP5 (human ovarian carcinoma) cells with an IC(50) of 38 nM."
sparser
"Indeed, we observed unprecedented single-molecule pairwise site-specific phosphorylation patterns of EGF-induced or in vitro autophosphorylated EGFR ( xref and xref ) by the colocalization analysis, although multiple labeling in a short sequence (<100 amino acids, not tested) still remains uncertain."
sparser
"In summary, results strongly suggest that PTP1B plays a role in the negative regulation of EGFR signaling in rat corneal endothelial cells, at least at the level of Tyr992 phosphorylation, and that inhibition of PTP1B activity increases both the duration of EGFR autophosphorylation and the relative number of cells entering the cell cycle."
sparser
"Anti-EGFR monoclonal antibodies like cetuximab and panitumumab block ligand-induced receptor activation, while small molecule EGFR inhibitors such as erlotinib, gefitinib and lapatinib compete with adenosine triphosphate (ATP) to bind the catalytic domain of the kinase, which in turn inhibits EGFR autophosphorylation and downstream signalling [ xref ]."
sparser
"Treatment of keratinocytes with rosiglitazone did not suppress epidermal growth factor receptor autophosphorylation, but inhibited signaling through the extracellular regulated kinase mitogen-activated protein kinase pathway without a concomitant effect on pathways that lead to c-jun activation."
sparser
"To assess whether the defect in the activation of the Akt-mTORC1 pathway by EGF in DKO MEFs occurred at the level of the receptor, we examined autophosphorylation of EGFR and the activity of EGFR by measuring phosphorylation of its physiological substrates phospholipase C–γ1 (PLC-γ1) and signal transducer and activator of transcription 5 (STAT5)."
sparser
"Mutations designed to disrupt the domain II/IV tether caused no apparent elevation in constitutive autophosphorylation of EGFR [ xref , xref ], although slight differences in dose-response relationships were seen for some EGF-dependent signals, consistent with increased ligand-binding affinity."
sparser
"Autophosphorylation of EGFR favors Y845 rather than Y1045 and Y1068 docking sites; autophosphorylated EGFR appears to be monomeric by anisotropy; non-liganded EGFR cycles via Rab11 endosomes unless it engages Cbl and then is sent to lysosomes due to ubiquitylation; perinuclear protein tyrosine phosphatase dephosphorylated recycling endosome-localized EGFR."
sparser
"In another trial, Townsley et al. found that erlotinib, a more potent EGFR tyrosine kinase inhibitor, effectively inhibited both EGFR autophosphorylation and phosphorylation of ERK but did not reduce proliferation, as measured by p27 and Ki-67/MIB-1, in colorectal cancer metastases ( xref ); however, no clinical responses were observed in 31 evaluable patients."
sparser
"Tumors cells containing the exon 19 deletion mutation demonstrate constitutive EGFR autophosphorylation only in the presence of gene amplification, whereas cells containing the L858R mutation demonstrate constitutive autophosphorylation regardless of amplification status ( xref )."
sparser
"Treatment of these cells with the MEK1 inhibitor blocked the EGF-induced migration of these cells and selectively prevented EGF-induced ERK1 and ERK2 phosphorylation without impacting other EGFdependent phosphorylation events, including the autophosphorylation of the EGF receptor (data not shown)."
sparser
"We then made use of the U87 and LN229 glioblastoma cell lines to further establish that tTG mediates the up-regulation of EGFR expression and signaling. xref (top two panels) shows that treatment of both U87 and LN229 cells with the tTG inhibitor MDC consistently reduced the basal levels of EGFR expression and activation, as read-out using an anti-pan-EGFR antibody and an anti-phospho-EGFR antibody that detects EGFR auto-phosphorylation, respectively."
sparser
"Down-regulation of cell surface EGF-R was demonstrated by results from several methods, namely the absence of EGF-R autophosphorylation in an immune complex kinase assay, the inability to iodinate EGF-R on the cell surface, the formation of endosomes containing EGF-R as detected by immunofluorescence, and the degradation of the metabolically [35S]Met-labeled fully processed 170K species of EGF-R. No effect on the initial synthesis of EGF-R was observed."
sparser
"These small molecules inhibit EGFR autophosphorylation and, thus, they inhibit receptor dimerization, and the downstream signaling that would have otherwise stimulated proliferation (through the activation of Erk) and anti-apoptotic mechanisms (through activation of Akt and Stat)."
sparser
"Tarceva is a commercial compound known to inhibit EGF-R autophosphorylation without affecting EGF-R expression or surface receptor density. xref No significant difference in total intensity levels of EGF-R between stimulated and Tarceva-inhibited cells were measured with respect to controls ( xref )."
sparser
"mAbs bind to the extracellular domain of the EGFR and compete with endogenous ligands to block the ligand-binding region and ligand-induced EGFR tyrosine kinase activation. xref TKIs reversibly compete with adenosine 5’ triphosphate (ATP) to bind to the intracellular catalytic domain of EGFR tyrosine kinase and inhibit EGFR autophosphorylation and downstream signalling. xref Various anti-EGFR agents, such as cetuximab, xref nimotuzumab, xref panitumumab, xref erlotinib xref and gefitinib, xref are used for treating OC."
sparser
"Previous measurements had shown that PNA -labelled EGFR undergoes autophosphorylation and internalizes upon EGF activation. xref The rather weak internalisation of EGFR observed here is probably due to coexpression with ErbB2, which has been reported to impair EGF stimulated endocytosis of EGFR. xref Both receptors responded more strongly to 20 min treatment with GA."
sparser
"Basal growth of MCF-7 cells was unaffected by co-administration of the growth factors EGF, TGF-alpha, IGF-I, and IGF-II, and the new agents did not inhibit EGFR and c-erbB2 autophosphorylation in cell lysates from MDA 468 or SkBr3 cells, respectively, suggesting that receptor tyrosine kinases are not targets for these compounds."
sparser
"Importantly, associated modeling studies suggest that the EGF receptor also cycles rapidly between phosphorylated and dephosphorylated states in the absence of activating ligand ( xref ), as predicted by the well-known observation that phosphatase inhibition using pervanadate or hydrogen peroxide rapidly enhances autophosphorylation (and activation) of EGFR and other RTKs."
sparser
"Recent detailed studies in two other cell types showed that the CaM inhibitors W-7, W-12, and W-13 inhibit the initial peak of ErbB1 autophosphorylation, but not the steady-state value observed for times >20 min ( xref ), as expected from our model. xref report an important control experiment: W-7, W-12, and W-13 do not inhibit the tyrosine kinase activity of a purified ErbB1 preparation."
sparser
"Moreover, the cytokine-stimulated tyrosine kinase activity assay confirmed VEGF induced tyrosine autophosphorylation of EGFR, AKT, and ERK1/2 in Human Umbilical Vein Endothelial Cells (HUVECs); however, such changes could be reversed in a concentration-dependent manner by the simultaneous administration of anlotinib at concentration of 2.5, 5.0, 10.0, and 15.0 (Fig. xref E)."
sparser
"In EGFR -altered samples, high EGFR autophosphorylation was observed, along with increased abundance and phosphorylation of pleckstrin homology-like domain family A member proteins (PHLDA1 and PHLDA3), transcription factor SOX9, cell adhesion protein CTNND2 (δ-catenin), and cell cycle proteins CDK6 and CDKN2C ( xref and xref )."
sparser
"Using the EGFR-overexpressing human epidermoid carcinoma of the vulva cell line, A431, we demonstrate herein that (a) RB24 and its derived species (e.g. RB14, ZR08) irreversibly inhibit EGFR autophosphorylation, (b) RB24 induced significant levels of DNA strand breaks, (c) sustained inhibition of EGFR by RB24 was associated with blockade of MAPK activation and c-fos gene expression, (d) RB24 induced irreversible cell growth inhibition with a 100-fold greater potency than Temodaltrade mark, a clinical methyltriazene."
sparser
"Cx is a chimeric mouse-human monoclonal IgG1 antibody that binds EGFR at its extracellular domain and blocks EGF-induced autophosphorylation of EGFR. xref It has preclinical activity in vitro and in vivo both as a single agent and in combination with cytotoxic compounds and RT in different human cancer models, including HNC. xref xref – xref Anti-EGFR antibody competes with EGFR ligands, resulting in internalization and degradation of the antibody-receptor complex and leading to the death of tumor cells also through the indirect mechanism of NK-dependent antibody mediated cytotoxicity [antibody dependent cell-mediated cytotoxicity (ADCC)]. xref , xref It also induces the dimerization and downregulation of EGFR, perturbs cell cycle progression, xref and inhibits tumor-induced angiogenesis. xref Beyond Cx, other anti-EGFR antibodies have been developed in HNSCC. xref Zalutumumab is a human monoclonal antibody against EGFR that has shown activity in preclinical models by blocking the EGFR signaling pathway and, as Cx, by stimulating ADCC. xref Panitumumab is a fully human anti-EGFR monoclonal antibody that effectively inhibits EGFR signaling similarly to Cx."
sparser
"In the present paper, we report (i) the effect of N,N-dimethylsphingosine as compared with lyso-glycosphingolipids and other sphingolipid breakdown products on EGF receptor autophosphorylation and (ii) demonstration of endogenous N,N-dimethylsphingosine synthesis and the virtual absence of unsubstituted sphingosine in A431 cells."
sparser
"EGFR autophosphorylation was suppressed at all EGF concentrations in ethanol-fed cells compared with pair-fed cells, without significant differences in total EGFR protein or EGFR tyrosine kinase activity detected in cell lysates, suggesting that intracellular factors suppressed EGFR function."
sparser
"The Wnt signaling pathway is highly activated in CCSCs and inhibition of the reactive protein in this pathway will block signal transduction, thereby affecting the growth of CCSCs and achieving the purpose of treating CRC. xref xref - xref High levels of Yap polypeptides are thought to be important factors in promoting the proliferation of CCSCs. xref High expression of Yap can cause the expansion of intestinal stem cell population and promote cancer cell proliferation, while the elimination of Yap can attenuate β-catenin and Notch signaling and inhibit cell proliferation and survival. xref In the HCT116 cell line, epidermal growth factor (EGF) was also found to be essential for maintaining stem cell proliferation. xref xref xref - xref Inhibition of autophosphorylation of EGF receptor (EGFR1) and downstream signaling pathway protein AKT and extracellular signal-regulated kinase ERK1/2 decreases proliferation and induces apoptosis in CCSCs. xref Conditional inactivation of the telomerase reverse transcriptase ( TERT ) gene in colonic epithelial cells of newborn mice can induce overexpression of colonic crypts in mice, causing an increase in mucosal thickness and an increase in the number of goblet cells. xref This change in the differentiation status of selective crypts suggests that deficiency of TERT induces the proliferation and behavior of CCSCs to lead to tumorigenesis."
sparser
"Furthermore, we demonstrate that EGF (i) increased the binding affinity of EGFR to Gab1 Tyr-627 and Shc Tyr-317 sites in purified GST fusion proteins approximately 4-6-fold, and (ii) EGF significantly enhanced the phosphorylation of these sites, relative to EGFR autophosphorylation, in cell lysates containing the full-length Gab1 and Shc proteins."
sparser
"The complete loss of high-affinity binding sites for EGF did not prevent EGF-dependent autophosphorylation of EGF-R. Hepatocytes from the rat liver tumors in the primary culture had two classes of EGF-R: high and low affinity ones, though their number had been twice less than in the normal hepatocytes."
sparser
"Next, we further tested whether Src activity is required for the EGFR's resistance to Erlotinib/TKIs under CS exposure by transiently over-expressing either DN-Src or CA-Src in A549 for 24h then subsequently incubating the cells with 1 μM Erlotinib for 30 minutes and exposing them to either EGF or CS, as before. xref shows that the DN-Src could sensibly improve the efficacy of Erlotinib in inhibiting EGFR auto-phosphorylation during CS exposure, compared to the unobstructed CS-induced EGFR Tyr phosphorlyation in cells expressing the CA-Src treated with Erlotinib ( xref )."
sparser
"Exposure to asbestos fibres causes EGFR aggregation, and the subsequent autophosphorylation and activation of EGFR activates both the RAS/RAF/MAPK pathway (which induces cell proliferation, metastasis, and invasion) ( xref ) and the PI3KCA/AKT/mTOR pathway, which leads to the inhibition of apoptosis ( xref )."
sparser
"Human malignant mammary, MCF-7, and squamous, A431, cells showed low baseline phospho-tyrosine levels of epidermal growth factor receptor, permitting reproducible dose-dependent stimulation of epidermal growth factor receptor autophosphorylation after exposure to epidermal growth factor."
sparser
"Gefitinib, which is a selective EGFR (ErbB1) tyrosine kinase inhibitor, prevents autophosphorylation of EGFR in various tumor cell lines and xenografts. xref The major hindrance to an effective anticancer activity of gefitinib is the resistance, which arises in the cells after repeated administration of gefitinib."
sparser
"Interestingly, HN5-R and FaDu-R cells remained sensitive or partially
sensitive to cetuximab-induced inhibition of cell signaling, as revealed by the
inhibition of EGFR autophosphorylation (in FaDu-R cells, but not apparent in
HN5-R cells) and reduced phosphorylation of Akt-S473 and Erk T202/Y204 (with
slight difference in the extents between FaDu-R and HN5-R cells), two important
signaling molecules downstream of EGFR ( xref )."
sparser
"While we observed substantial overexpression only in approximately 20% of HNSCC, we also observed strong discrepancies between EGFR protein expression and auto-phosphorylation in HNSCC cell lines as well as in tumor specimens using Western blot and SH2-profiling; for the majority of HNSCC EGFR expression therefore seems not to be correlated with EGFR auto-phosphorylation."
sparser
"Mechanisms of EGFR resistance continue to be a topic of interest in different tumor types including SCCHN where several possible mechanisms have been described including a deletion mutation of exon 2–7 of the extracellular ligand-binding domain of EGFR leading to a truncated form of EGFR (EGFR vIII) that is auto-phosphorylated in a ligand-independent way."
sparser
"In lung cancer cells with EGFR mutations, gefitinib and erlotinib selectively bind to the tyrosine kinase region of the intracellular domain of EGFR and significantly attenuate the autophosphorylation of EGFR, reduce the subsequent activation of the PI3K/Akt/mTOR and RAS/RAF/MAPK pathways, and inhibit cell proliferation and promote apoptosis. xref Irreversible inhibitors also show potent activity against proliferation in cells with activating EGFR mutations and gatekeeper T790M mutations by binding covalently to EGFR. xref "
trips
"Following 2-h treatment, gefitinib significantly inhibited EGFR autophosphorylation and subsequent downstream signaling pathway through Erk and Akt, and induced accumulation of cells in the G0/G1 phase of the cell cycle at 24-h, accompanied by a concomitant increase in p21 transcript and increased expression of p27."
sparser
"The possible explanation for this result might be that as a small molecule tyrosine ammonia kinase inhibitor, erlotinib can prevent the autophosphorylation of EGFR.[ xref ]The inhibition of cell proliferation, angiogenesis, invasion, and metastasis and the inducement of apoptosis eventually can exert antitumor effects.[ xref ]The experiment of Gu et al[ xref ]indicates that the inhibition of tumor growth and metastasis of sorafenib is achieved by blocking mitogen-activated protein kinases/extracellular signal-regulated kinases/signal transducer and activator of transcription 3 and phosphatidylinositol-3-kinase/protein kinase B/signal transducer and activator of transcription 3 signaling pathways, both of which are different in tumor suppression mechanism which plays a synergistic effect in inhibition of AHCC."
sparser
"Both in vitro and in vivo , ZD6474 effectively inhibited tyrosine autophosphorylation of EGFRvIII as well as protein phosphorylation of Stat3 and Akt and protein expression of Bcl-X L in GBM8 cells that retain EGFRvIII expression in vitro and in vivo compared with GBM14 cells lacking EGFRvIII ( xref )."
sparser
"Studies conducted in both RCEC ( xref ) and HCEC ( xref ) have demonstrated that specific inhibition of PTP1B activity was able to sustain EGF-induced tyrosine autophosphorylation of the EGF receptor and increase the number of cells entering the cell cycle, indicating the possibility that the number of proliferating HCEC could be increased by suppressing the down-regulation of growth factor signaling."
sparser
"To strip the IF antibodies from the
single-molecule surface, we applied a low-pH/detergent-based erasing
buffer after SiMBlot assay of a model protein such as in vitro autophosphorylated epidermal growth factor receptor (EGFR, a transmembrane
receptor protein for the epidermal growth factors (EGFs) family of
extracellular ligands) xref with anti-pTyr
primary antibody and an Alexa Fluor 555-labeled secondary antibody."
sparser
"Following 2-h treatment, gefitinib significantly inhibited EGFR autophosphorylation and subsequent downstream signaling pathway through Erk and Akt, and induced accumulation of cells in the G0/G1 phase of the cell cycle at 24-h, accompanied by a concomitant increase in p21 transcript and increased expression of p27."
sparser
"EGFR is then auto-phosphorylated or trans-phosphorylated at specific tyrosine residues for its activation, resulting in the activation of multiple downstream signaling cascades, including PI3K/Akt, and ERK, ultimately leading to increased cell proliferation and the prevention of programmed cell death xref ."
sparser
"Using a monoclonal antibody prepared against a synthetic peptide representation of the Y1173 EGF receptor autophosphorylation site, we have provided evidence that, unexpectedly, the deduced epitope, E/H L -pY-L/H B (where H L - is hydrophilic and H B is hydrophobic) is highly redundant within the cytoplasmic domain."
sparser
"From the independency between autophosphorylation sites, we conjecture that EGFR kinase activity has no inherent selectivity to recognize prior autophosphorylation of EGFR, explaining why EGF-induced EGFR on cell membrane was mostly mono-phosphorylated and rarely multi-phosphorylated ( xref )."
sparser
"T. gondii induces prolonged EGFR autophosphorylation and activation of its downstream molecule Akt through a cascade that consists of the cytosolic serine/threonine kinases protein kinase C α (PKCα) and PKCβ that cooperate to sustain Src activation that drives prolonged EGFR autophosphorylation ( xref ; xref )."
sparser
"Three samples had fusions between EGFR and intergenic or intronic chromosome 7 regions that are predicted to remove the EGFR autophosphorylation domain and are likely to be oncogenic ( xref ). xref Fusions involving genes encoding receptor tyrosine kinases were predominantly a feature of lower-grade gliomas with wild-type IDH ; only two lower-grade gliomas with an IDH mutation and no 1p/19q codeletion harbored such fusions (involving PDGFRA and MET ), and none were identified among lower-grade gliomas with an IDH mutation and 1p/19q codeletion."
trips
"Based on these results, we conclude that TPA-induced AP-1 activation requires the basal level-EGFR protein, but not EGFR tyrosine kinase and EGFR autophosphorylation at tyrosine(1173), whereas both EGFR tyrosine kinase and EGFR autophosphorylation at Y(1173) play a critical role in EGF-induced AP-1 activation."
sparser
"Exposure of cells to EGF resulted in a rapid EGFR autophosphorylation, at the Tyr 1045 site, which provides a docking site for the ubiquitin ligase c-Cbl, resulting in ubiquitination of the EGFR and removal of the EGFR via endocytosis from the cell surface into an early endosomal compartment ( xref )."
sparser
"Using the EGFR-overexpressing human epidermoid carcinoma of the vulva cell line, A431, we demonstrate herein that (a) RB24 and its derived species (e.g. RB14, ZR08) irreversibly inhibit EGFR autophosphorylation, (b) RB24 induced significant levels of DNA strand breaks, (c) sustained inhibition of EGFR by RB24 was associated with blockade of MAPK activation and c-fos gene expression, (d) RB24 induced irreversible cell growth inhibition with a 100-fold greater potency than Temodal™, a clinical methyltriazene."
sparser
"We investigated the effects of lidocaine (40-4000 microM) on proliferation of a human tongue cancer cell line, CAL27, which has a high level of EGFR expression, and also examined the effect of lidocaine on epidermal growth factor (EGF)-stimulated autophosphorylation of EGFR in CAL27 cells."
sparser
"To test this hypothesis, we used the reversibility assay previously described ( xref ; xref ) according to which the cells were treated with the drug for 90 min and the culture medium repeatedly removed and replaced three times after treatment, after which EGFR autophosphorylation was measured."
sparser
"On the other hand, activation of EGFR by its ligand (epidermal growth factor and transforming growth factor-α) induces autophosphorylation of EGFR at distinct and overlapping tyrosine residues (including Tyr 992 , Tyr 1068 , Tyr 1086 , Tyr 1148 , and Tyr 1173 )( xref , xref ); these phosphorylated tyrosine residues serve as docking sites for a range of adaptor proteins, whose recruitment leads to activation of the downstream cell survival signaling cascade including the Akt pathway."
sparser
"Similarly, no detectable constitutive EGFR tyrosine phosphorylation of L858R/CYF10, Ex19Del/CYF10 or Ex20Ins/CYF10 EGFR mutants was found (Fig. xref b , lanes 6, 8 and 10), confirming that all C‐terminal phosphorylation sites were mutated and that CYF10 EGFR mutants lack autophosphorylation."
sparser
"Interestingly, YM155 has been shown to reduce EGFR expression and tumor cell proliferation and survival in pancreatic cancer xref as well as EGFR-positive non-small cell lung cancer, in which YM155 was found to be synergistic with afatinib xref and other EGFR inhibitors xref , to reverse resistance to the EGFR inhibitor erlotinib in EGFR-mutant lung cancer xref , and to inhibit EGFR autophosphorylation which promotes lung cancer stemness xref ."
sparser
"Furthermore, the epidermal growth factor receptor (EGFR) signaling pathway plays an important role in the regulation of homeostasis, such as cell growth, differentiation, and carcinogenesis. [ xref – xref ] Altered EGFR expression or EGFR mutation has been reported in esophageal cancer and correlated with poor patient prognosis and inferior response to therapy. [ xref – xref ] Moreover, radiation can induce autophosphorylation of EGFR protein and downstream substrates, which then leads to tumor resistance to radiotherapy, and tyrosine kinase inhibitors can prevent this autophosphorylation of EGFR."
sparser
"In this study, we demonstrated that a basic sPLA(2) inhibits epidermal growth factor (EGF)-induced EGF receptor activation, as determined by autophosphorylation of EGF receptor, EGF-activated phospholipase D (PLD) activity, and phospholipase C-gamma(1) (PLC-gamma(1)) tyrosine phosphorylation in a human epidermoid carcinoma cell line, A-431."
sparser
"Serum starved GIV-wt, GIV-FA, and control HeLa cells were stimulated with EGF, and EGFR autophosphorylation was assessed at Y992, Y1045, and Y1068, (docking sites of the SH2 adaptors, PLCγ1, cCbl, and Grb2) and at Y845 (the substrate for c-Src kinase that triggers mitosis; xref ), using site-specific phospho-Tyr antibodies ( xref A)."
sparser
"There was little effect of 31 on the autophosphorylation of EGFR, so we hypothesized that there might be involvement of other kinases (that we previously found were potently inhibited by AppCCl 2 p in vitro) and chose to investigate the phosphorylation of STAT3 (signal transducer and activator of transcription 3; xref )."
sparser
"Since it has been reported that it is the PIP5KIβ and not the PIP5KIα isoform that is involved in EGFR internalization, it is unlikely that the siRNA-mediated reduction of the PIP5KIα isoform led to a decrease in EGFR autophosphorylation due to a decreased cell surface receptor density."
sparser
"Growth factors such as transforming growth factor α and epidermal growth factor induce EGFR homodimerization or heterodimerization with other members of the erbB family, including HER2/ neu (erbB2), HER3 (erbB3), and HER4 (erbB4), followed by EGFR autophosphorylation at specific tyrosine sites."
sparser
"When tested in Ba/F3 cells expressing EGFR L858R/T790M/C797S , compound 11 resulted significantly more potent than osimertinib at inhibiting both EGFR autophosphorylation and proliferation, even if the inhibition of EGFR autophosphorylation by compound 11 in Ba/F3 cells was not long lasting."