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Receptor Protein-Tyrosine KinasesProto-Oncogene Proteins c-kitNeuregulin-1Protein-Tyrosine KinasesNeuregulinsReceptor, erbB-3Proto-Oncogene ProteinsTyrosineSignal TransductionReceptor, Epidermal Growth FactorReceptor, erbB-2Genes, erbBReceptor-Like Protein Tyrosine Phosphatases, Class 4PhosphorylationProtein Tyrosine PhosphatasesEpidermal Growth FactorMolecular Sequence DataAmino Acid SequenceProtein Kinase InhibitorsCell LinePhosphatidylinositol 3-KinasesMutationTransfectionsrc-Family KinasesTumor Cells, CulturedBase SequenceMAP Kinase Signaling SystemReceptors, Cell SurfaceProtein-Serine-Threonine KinasesProtein KinasesAntigens, CD45Oncogene Proteins v-erbBPhosphotyrosineQuinazolinesEnzyme ActivationCell Line, TumorProtein Structure, TertiaryCalcium-Calmodulin-Dependent Protein KinasesProtein BindingMembrane ProteinsGenisteinEnzyme InhibitorsMitogen-Activated Protein Kinase 1Recombinant Fusion ProteinsCell MembraneTyrphostinsCells, CulturedPhosphoproteinsPyrimidinesProtein Kinase CLymphocyte Specific Protein Tyrosine Kinase p56(lck)Blotting, WesternMitogen-Activated Protein Kinase 3Tyrosine 3-MonooxygenaseProto-Oncogene Proteins pp60(c-src)Mitogen-Activated Protein KinasesBinding SitesKineticsProto-Oncogene Proteins c-ablIntracellular Signaling Peptides and ProteinsRecombinant Proteinssrc Homology DomainsAntineoplastic Agentsp38 Mitogen-Activated Protein KinasesProto-Oncogene Proteins c-aktSequence Homology, Amino AcidCyclic AMP-Dependent Protein KinasesAdaptor Proteins, Signal Transducing3T3 CellsRNA, MessengerMitogen-Activated Protein Kinase KinasesLigandsGenes, erbB-2Proto-Oncogene Proteins c-fynFocal Adhesion Kinase 2Cell DivisionMutagenesis, Site-DirectedExtracellular Signal-Regulated MAP KinasesCystic Fibrosis Transmembrane Conductance RegulatorCell ProliferationBreast NeoplasmsPrecipitin TestsApoptosisJNK Mitogen-Activated Protein KinasesFocal Adhesion Protein-Tyrosine KinasesBenzamidesImmunoblottingFocal Adhesion Kinase 1fms-Like Tyrosine Kinase 3Models, MolecularModels, Biologicalp21-Activated KinasesCloning, MolecularJanus Kinase 2PiperazinesDimerizationQuinonesCOS CellsIsoenzymesVanadates
Her1HER2ErbB1ErbB2ProteinPhosphorylationExtracellular domainErbB3ResiduesLigandsHuman EpidermalInhibitorsIntracellular tyrosine kinaseEpidermal growthCell proliferationDimerizationProteinsPathwayAutophosphorylationAntibodyRTKsHer3TumorsErbB4GlycoproteinSingle transmembraneSignal transductionAnti-EGFRMutationsOncogeneEpithelialCancersConsistsBindsMetastaticAmplificationTherapiesMAPKMolecularRegulatesPoor prognosisCancerHumansTumor cellDomain
Her18
  • HER1-HER1 and HER1-HER2 dimers, and not HER1-HER3 dimers, ii) HER1-HER2 and HER2-HER3 dimers both contribute significantly to HER2 activation with the EGFR expression level determining the relative importance of these species, and iii) the HER2-HER3 dimer is largely responsible for HER3 activation. (researchhunt.com)
  • The HER Alosetron family is comprised of four unique receptors: EGFR (also known as HER1 or ErbB-1) HER2 (ErbB-2 Neu) HER3 (ErbB-3) and HER4 (ErbB-4). (ecolowood.com)
  • EGFR antibody recognizes epidermal growth factor receptor (EGFR, also known as HER1 in humans), a receptor tyrosine kinase with a predicted molecular weight of 134 kDa. (genetex.com)
  • EGFR (Epidermal growth factor receptor, HER1, ErbB1) is encoded by the EGFR gene located on chromosome 7 in humans. (thermofisher.com)
  • HER2 is so named because it has a similar structure to human epidermal growth factor receptor, or HER1. (iiab.me)
  • Also, the growth-inhibitory effects of HER1/2 tyrosine kinase inhibitors (TKIs) were previously found to be attenuated in the presence of heregulin, which is a high-affinity combinatorial ligand for HER3. (biomedcentral.com)
  • Failure to reverse breast cancer progression despite apparent inhibition of HER1 and HER2 kinase functions in cell-based assays as well as in patient tissues and tumours is an enigma that is not yet resolved [ 6 ]. (biomedcentral.com)
  • Although it is kinase defective, the HER family member HER3 can be phosphorylated by HER1 or HER2, and HER3 can couple with the pro-survival phosphatidylinositol-3-OH kinase (PI[ 3 ]K)/Akt pathway directly whereas HER1 and HER2 cannot [ 5 ] (Figure 1 ). (biomedcentral.com)
HER224
  • The ErbB protein family consists of 4 members ErbB-1, also named epidermal growth factor receptor (EGFR) ErbB-2, also named HER2 in humans and neu in rodents ErbB-3, also named HER3 ErbB-4, also named HER4 v-ErbBs are homologous to EGFR, but lack sequences within the ligand binding ectodomain. (wikipedia.org)
  • In particular, HER2 and HER3 are over-expressed in 23277-43-2 IC50 a number of tumors, and their expression levels are associated with abnormal growth and poor clinical prognosis. (researchhunt.com)
  • Overexpression of EGFR, HER2 and HER3 is associated with decreased survival in cancer, while HER4 overexpression is correlated with increased survival [8], [9]. (researchhunt.com)
  • While this has led to the development of a range of therapeutics targeting the HER2 receptor [15], the use of these drugs can often lead to resistance through a diverse set of mechanisms [16]. (researchhunt.com)
  • HER2 does not have any identified ligand an undeniable fact explained from the structure from the extracellular area from the receptor which is already in an activated conformation and does not allow ligand docking. (ecolowood.com)
  • ErbB receptors comprise a family of four RTKs (EGFR/ErbB1, Her2/ErbB2, Her3/ErbB3 and Her4/ErbB4) with important roles in normal cell physiology and in cancer 1 . (nature.com)
  • One such target of these novel therapies has been the human epidermal growth factor receptor 2 ( HER2 ) gene. (degruyter.com)
  • It is also frequently called HER2 (from human epidermal growth factor receptor 2 ) or HER2/neu . (iiab.me)
  • HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. (iiab.me)
  • Molecular cloning of the gene showed that HER2, Neu, and ErbB-2 are all encoded by the same orthologs. (iiab.me)
  • [10] [11] HER2 can heterodimerise with any of the other three receptors and is considered to be the preferred dimerisation partner of the other ErbB receptors. (iiab.me)
  • Recent evidence has implicated HER2 signaling in resistance to the EGFR-targeted cancer drug cetuximab . (iiab.me)
  • HER2 is found in a variety of tumours and some of these tumours carry point mutations in the sequence specifying the transmembrane domain of HER2. (iiab.me)
  • Receptor tyrosine-protein kinase ERBB-2 (HER2 - human epidermal growth factor receptor 2) is considered as a marker of aggressiveness in the case of breast cancer in primary tumours as well as in corresponding metastases. (biomedres.us)
  • ERBB2 (also HER2) is a transmembrane receptor that is a member of the ERBB family of receptor tyrosine kinases. (cornell.edu)
  • Amplification of the human epidermal growth factor receptor 2 ( HER2 ) gene and overexpression of the HER2 protein is found in 15%-20% of patients with gastric and gastroesophageal junction cancer. (wjgnet.com)
  • Inside the nucleus, HER family members (EGFR, HER2, and HER3) have been shown to function as co-transcriptional activators for various cancer-promoting genes. (plos.org)
  • The ErbB/HER family of receptor tyrosine kinases (RTKs) consists of four family members: the epidermal growth factor receptor (EGFR/ErbB1), HER2 (ErbB2/Neu), HER3 (ErbB3), and HER4 (ErbB4). (plos.org)
  • The HER2 receptor does not bind to any known ligands, however, its dimerization arm is innately positioned in an open conformation. (plos.org)
  • Although neither kinase-dead human epidermal growth factor receptor (HER)3 nor orphan HER2 can be activated by HER-related ligands on their own, the formation of HER2/HER3 heterodimers creates the most mitogenic and transforming receptor complex within the HER (erbB) family of transmembrane receptor tyrosine kinases. (biomedcentral.com)
  • Pioneering studies showed that high expression of kinase-dead HER3 can predict early escape from the anti-HER2 monoclonal antibody trastuzumab. (biomedcentral.com)
  • in particular, HER3 signalling buffered against incomplete inhibition of HER2 kinase activity has been suggested to be the mechanism that allows HER2 over-expressing breast cancer cells to escape HER TKIs. (biomedcentral.com)
  • It remains to be elucidated whether reactivation of HER3 signalling can also account for the poor efficacy of HER TKIs in treating breast carcinomas that contain low overall levels of HER2 receptors. (biomedcentral.com)
  • However, it appears that regardless of the mechanism that triggers the formation of oncogenic HER2/HER3 heterodimers (HER2 over-expression or overall low HER2 but high levels of the HER3 ligand heregulin), HER3 transphosphorylation is a common response of breast cancer cells upon treatment with current inhibitors of the HER receptor tyrosine kinase network. (biomedcentral.com)
ErbB12
  • Notably, the ErbB1 and ErbB4 are the two most studied and intact among the family of ErbB proteins, Which forms functional intracellular tyrosine kinases. (wikipedia.org)
  • Interestingly, this same three amino acid signal has been found in ErbB4 and ErbB1 (EGFR). (rndsystems.com)
ErbB214
  • ErbB2 has no known binding ligand and absent of an active kinase domain in ErbB3 make this duo preferable to form heterodimers & share each other's active domains to activate transphosphorylation of the tyrosine kinases. (wikipedia.org)
  • HER-2 (ErbB2) is a 185-kDa transmembrane tyrosine kinase with extensive homology to the epidermal growth factor receptor (EGFR). (touchoncology.com)
  • EGFR belongs to the HER/ERbB family of proteins that includes three other receptor tyrosine kinases, ERbB2, ERbB3, ERbB4. (thermofisher.com)
  • Typically, heterodimerization with ErbB2 forms the high affinity receptor complex. (rndsystems.com)
  • Because ErbB3 contains a defective kinase domain, the kinase domain of ErbB2 is responsible for initiating the tyrosine phosphorylation signal through the heterodimeric receptor. (rndsystems.com)
  • Here we exploit the multiplexing capabilities of Exchange-PAINT, a multiplexed variant of DNA-PAINT 14 , to image simultaneously five RTKs (EGFR, ErbB2, ErbB3, IGF-1R and Met) at endogenous levels of expression in BT20 cancer cells and to examine how receptor distribution changes following ligand stimulation. (nature.com)
  • Receptor tyrosine-protein kinase erbB-2 , also known as CD340 (cluster of differentiation 340), proto-oncogene Neu , Erbb2 (rodent), or ERBB2 (human), is a protein that in humans is encoded by the ERBB2 gene. (iiab.me)
  • The enhancement in metastatic properties was also found to occur via activation of ERBB2 receptor signaling pathways [2]. (biomedres.us)
  • Somatic mutations in ERBB2 have been identified in a series of tumors including lobular breast, lung adenocarcinoma, and gastric cancers, among others, with recurrent hotspot alterations in both the extracellular and kinase domains. (cornell.edu)
  • In vitro studies have shown that this specific variant is associated with constitutive kinase activation and is associated with sensitivity to some ERBB2 inhibitors and therefore, it may represent a targetable mutation in some clinical settings. (cornell.edu)
  • Non-small-cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV_G/C mutation are sensitive to the dual-specific epidermal growth factor receptor and ERBB2 inhibitor HKI-272. (cornell.edu)
  • Formalin-fixed, paraffin-embedded human Breast Carcinoma stained with HER-2 Mouse Monoclonal Antibody (ERBB2/3078). (neobiotechnologies.com)
  • SDS-PAGE Analysis Purified HER-2 Mouse Monoclonal Antibody (ERBB2/3078). (neobiotechnologies.com)
  • Analysis of Protein Array containing more than 19,000 full-length human proteins using HER-2 Mouse Monoclonal Antibody (ERBB2/3078). (neobiotechnologies.com)
Protein36
  • The total-ErbB-2 antibody supplied in the FACE ErbB-2 Kits recognizes ErbB-2 protein regardless of its phosphorylation site. (activemotif.com)
  • ErbB protein family signaling is important for development. (wikipedia.org)
  • The figure below shows the tridimensional structure of the ErbB family proteins, using the pdb files 1NQL (ErbB-1), 1S78 (ErbB-2), 1M6B (ErbB-3) and 2AHX (ErbB-4): The four members of the ErbB protein family are capable of forming homodimers, heterodimers, and possibly higher-order oligomers upon activation by a subset of potential growth factor ligands. (wikipedia.org)
  • The EGFR is definitely a 170-kd protein encoded by a 110-kb-long gene localized in the short arm of chromosome 7. (ecolowood.com)
  • Three major intracellular signaling pathways linked to EGFR activation have been identified: the Ras-Raf-mitogen-activated protein (MAP) kinase pathway the phosphatidylinositol 3-kinase (PI-3 K)/Akt pathway and the Janus-kinase/signal transducer and activator of transcription (Jak2/STAT3) pathway. (ecolowood.com)
  • ErbB is a transmembrane receptor tyrosine protein kinase, ErbB receptor family. (cancer-research-network.com)
  • EGFR (epidermal growth factor receptor) is a transmembrane protein and receptor for members of the epidermal growth factor (EGF) family of extracellular protein ligands. (promab.com)
  • Recombinant protein encompassing a sequence within the C-terminus region of human EGFR. (genetex.com)
  • The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. (genetex.com)
  • This protein is a receptor for members of the epidermal growth factor family. (genetex.com)
  • EGFR is a cell surface protein that binds to epidermal growth factor. (genetex.com)
  • Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. (genetex.com)
  • EGFR antibody [GT133] detects EGFR protein at cell membrane on human colon carcinoma by immunohistochemical analysis. (genetex.com)
  • Phosphorylation of EGFR at Y1086 specifically allows binding of the adaptor protein GRB2, leading to activation of the MAPK pathway. (thermofisher.com)
  • Mutations in the EGFR gene are associated with lung cancer and multiple alternatively spliced transcript variants encode different protein isoforms of EGFR have been found. (thermofisher.com)
  • HER-2/neu , also known as c-erbB-2/neu , is an oncogene located in chromosome 17 which encodes HER-2/neu, a transmembrane protein belonging to the EGFR family. (degruyter.com)
  • The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases. (nature.com)
  • Substitution of a valine for a glutamic acid in the transmembrane domain can result in the constitutive dimerisation of this protein in the absence of a ligand. (iiab.me)
  • Like sorafenib, lapatinib is a protein kinase inhibitor shown to decrease tumor-causing breast cancer stem cells. (hmdb.ca)
  • ELISA plate pre-coated by 1 μg/ml (100 μl/well) Human EGFR protein, His tagged protein ( PME100099 ) can bind Rabbit anti-EGFR monoclonal antibody (clone: DM128) in a linear range of 0. (dimabio.com)
  • EGFR protein is highly expressed on the surface of Expi293 cell membrane. (dimabio.com)
  • Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein and member of the protein kinase superfamily that regulates cell growth and differentiation. (biolegend.com)
  • Recognizes a protein of 185kDa, which is identified as c-erbB-2/HER-2/neu. (neobiotechnologies.com)
  • c-erbB-2/HER-2 protein is over-expressed in a variety of carcinomas especially those of breast and ovary. (neobiotechnologies.com)
  • Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. (neobiotechnologies.com)
  • The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. (cancerindex.org)
  • Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. (univ-amu.fr)
  • G-protein-coupled receptors (GPCRs), the largest family of signalling receptors, as well as important drug targets, are known to activate extracellular-signal-regulated kinase (ERK)-a master regulator of cell proliferation and survival1. (bvsalud.org)
  • We further identify an endosomally localized non-canonical signalling axis comprising Gαs, RAF and mitogen-activated protein kinase kinase, resulting in endosomal ERK activity that propagates into the nucleus. (bvsalud.org)
  • It also induced glycogen synthase kinase-3ß (GSK3ß) while inhibited protein phosphatase 2A (PP2A) phosphorylation. (bvsalud.org)
  • ELAC1 has been in the use and may as define as an RNase Z. In pyrophosphates subfamilies are transcribed from coupling tubules in the function by a two receptor chromatin that appears ultraviolet from protein threatening( reviewed in Popow et al. (evakoch.com)
  • Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases. (umbc.edu)
  • The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). (umbc.edu)
  • PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. (umbc.edu)
  • Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. (bioss.com.cn)
  • an adapter protein coupling the receptor to downstream signaling pathways. (bioss.com.cn)
Phosphorylation9
  • Each kit contains a total-ErbB-2 antibody that recognizes ErbB-2 regardless of its phosphorylation state. (activemotif.com)
  • Flow chart of the FACE in cell Western method that uses a cell based ELISA to measure the levels of the native and phospho forms of signaling proteins and kinases that are activated by phosphorylation. (activemotif.com)
  • The intracellular/cytoplasmic region of the ErbB receptor consists mainly of three subdomains: A juxtamembrane with approximately 40 residues, a kinase domain containing approximately 260 residues and a C-terminal domain of 220-350 amino acid residues that become activated via phosphorylation of its tyrosine residues that mediates interactions of other ErbB proteins and downstream signaling molecules. (wikipedia.org)
  • Following dimerization there is increased intracellular kinase activity of the receptor through a proximity effect resulting in phosphorylation of critical tyrosine residues on the cytoplasmic domain which then triggers the signal transduction cascade. (ecolowood.com)
  • Phosphorylation of EGFR at certain residues is also mediated by Src-non-receptor kinase. (thermofisher.com)
  • This process leads to the activation of each receptors' tyrosine kinase and the subsequent phosphorylation of tyrosine residues located on their C-terminal tails. (plos.org)
  • ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). (univ-amu.fr)
  • These two levels serve degraded by a phosphorylation including at least 6 membranes in a such tail that both leaves the 2' disorder ubiquitination and adducts the 3' heart to the 5' cell. (evakoch.com)
  • Unlike other tyr kinases, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. (umbc.edu)
Extracellular domain8
  • The ability ('+') or inability ('-') of each growth factor to activate each of the ErbB receptors is shown in the table below: The dimerization occurs after ligand bind to the extracellular domain of the ErbB monomers and monomer-monomer interaction establishes activating the activation loop in a kinase domain, that activates the further process of transphosphorylation of the specific tyrosine kinases in the kinase domain of ErbB's intracellular part. (wikipedia.org)
  • While it has been recognised for some time that overexpression of HER-2 is a poor prognostic factor in breast cancer, it was the advent of trastuzumab, a humanised monoclonal antibody directed against the extracellular domain of HER-2, that has allowed clinicians to better understand the natural history of HER-2-positive metastatic breast cancer. (touchoncology.com)
  • Once the ligand binds to the extracellular domain the receptor undergoes a conformational change of this region which allows homodimerization or heterodimerization with another activated receptor of the HER family. (ecolowood.com)
  • Disruption of EGFR signaling by blocking the EGFR-binding site on the extracellular domain of the receptor or inhibiting intracellular tyrosine kinase activity prevents the growth of EGFR-expressing tumors and improves patient outcomes. (promab.com)
  • EGFR is a transmembrane receptor and binding of its cognate ligands such as EGF (Epidermal Growth Factor) and TGF alpha (Transforming Growth Factor alpha) to the extracellular domain leads to EGFR dimerization followed by autophosphorylation of the tyrosine residues in the cytoplasmic domain. (thermofisher.com)
  • Human ErbB4 consists of 1308 amino acids (aa) with a 25 aa signal sequence, a 626 aa extracellular domain, a 24 aa transmembrane region, and a 633 aa cytoplasmic domain. (rndsystems.com)
  • This study aimed to identify novel genetic variants in the CR2 extracellular domain of the epidermal growth factor receptor (EGFR) in healthy individuals and patients with six different types of adenocarcinoma, in Arabian peninsula populations. (biomedcentral.com)
  • Structure of the extracellular domain of human epidermal growth factor (EGF) receptor in an inactive (low pH) complex with EGF. (embl.de)
ErbB33
  • Tumor-specific apoptosis caused by deletion of the ERBB3 pseudo-kinase in mouse intestinal epithelium. (nature.com)
  • We focused our research on the nucleolar function that a specific member of EGFR family, the ErbB3 receptor, plays in glioblastoma, a tumor without effective therapies. (biomedcentral.com)
  • These results highlight the potential role for the nucleolar ErbB3 receptor, as a new target in glioblastoma. (biomedcentral.com)
Residues6
  • The FACE ErbB-2 (Y877) Kit contains a phospho-ErbB-2 antibody that was raised in rabbit against a synthetic phospho-peptide corresponding to residues surrounding phosphorylated Tyr877 of human ErbB-2 and recognizes ErbB-2 only when phosphorylated at Tyr877. (activemotif.com)
  • This structure is made up of an extracellular region or ectodomain or ligand binding region that contains approximately 620 amino acids, a single transmembrane-spanning region containing approximately 23 residues, and an intracellular cytoplasmic tyrosine kinase domain containing up to approximately 540 residues. (wikipedia.org)
  • Dimerisation results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways. (iiab.me)
  • Phosphorylated tyrosine residues recruit various intracellular adaptor and effector molecules that result in the propagation of growth promoting signal transduction cascades [1] , [2] . (plos.org)
  • In the tethered conformation, EGFR ectodomain II and IV are folded into each other's forming the hairpin loop of domain II spanning residues 240-260 and interacts with C1IVc and C1IVd modules of domain IV (spanning residues 561-569 and 572-585, respectively). (biomedcentral.com)
  • Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. (bioss.com.cn)
Ligands9
  • Although, ErbB-2 does not have any known high-affinity ligands, its kinase activity can be activated without ligand by either overexpression or heteroassociation with other members of the ErbB family. (activemotif.com)
  • Its structure consists of an extracellular ligand-binding website a Alosetron single transmembrane hydrophobic helix and a cytoplasmic carboxy-terminal website to which tyrosine kinase activity is definitely limited.1 HER receptors are usually located in the basolateral membrane of the epithelial cells where they can interact with their ligands present in the stroma thus mediating signaling between the epithelium and the extra-cellular matrix. (ecolowood.com)
  • The ligands to HER receptors (also known as epidermal growth factor [EGF] family of growth factors) are characterized by the presence of an EGF-like website (composed of three disulfide-bonded intramolecular organizations which confer binding specificity) and extra structural motifs (such as for example immunoglobulin-like domains heparin-binding sites and glycosilation sites). (ecolowood.com)
  • They may be created as transmembrane precursors and could become subdivided into three organizations according with their affinity for just one or even more HER receptors: the 1st group includes ligands that bind specifically to EGFR (e.g. (ecolowood.com)
  • As ErbB-family ligands and receptors are highly expressed within the stem-cell niche 7 , we hypothesize that strong endogenous regulators must control the pathway in the stem-cell compartment. (nature.com)
  • Classically, HER family members function from the cell surface, where binding to cognate ligands can induce receptor homo- or hetero-dimerization with other HER family receptors [3] . (plos.org)
  • Despite significant promiscuity between other Eph family members and the ephrin ligands, the single physiologically-relevant ligand of the EphB4 receptor is ephrin-B2 [ 2 ]. (oncotarget.com)
  • Indeed, upon binding to ligands like EGF or TGF-α, the EGFR undergoes autophospholrylation that leads to the activation of several signal-transduction cascades, and cell cycle-progression [ 4 ]. (biomedcentral.com)
  • Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. (bioss.com.cn)
Human Epidermal4
Inhibitors11
  • If ultimately shown to reduce the risk of oral tumor chemoprevention with EGFR inhibitors may significantly reduce morbidity and possibly mortality from HNSCC. (ecolowood.com)
  • DelveInsight's "EGFR Inhibitors-Induced Skin Disorders Market Insights, Epidemiology, and Market Forecast-2032" report delivers an in-depth understanding of the EGFR Inhibitors-Induced Skin Disorders, historical and forecasted epidemiology as well as the EGFR Inhibitors-Induced Skin Disorders market trends in the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom) and Japan. (guwahatimail.in)
  • Up to 90% of cancer patients treated with EGFR inhibitors have skin adverse reactions. (guwahatimail.in)
  • Selective compounds have been developed that target either the extracellular ligand-binding region of the EGFR (including a number of monoclonal antibodies [MAbs], immunotoxins, and ligand-binding cytotoxic agents) or the intracellular tyrosine kinase region (including various small-molecule inhibitors). (medscape.com)
  • Inactivation of EGFR with selective inhibitors significantly reduces ERK2 activation, c-fos mRNA expression and cell proliferation. (signalchem.com)
  • Recently, highly targeted small-molecule agents, such as tyrosine kinase inhibitors (TKI), open a new avenue for RA therapy with improved clinical responses ( Koenders and Van DenBerg, 2015 ). (frontiersin.org)
  • Bortezomib restores expression of FoxO3a in imatinib resistant T315I cells The T315I BCR ABL mutation frequently occurs in CML patients that are resistant to imatinib, and even remains refractory to the more potent second generation kinase inhibitors. (mi-rna.com)
  • Several of these have undergone clinical trials, including low-molecular-weight inhibitors with highly selective and reversible tyrosine kinase inhibiting properties [ 1 - 5 ]. (biomedcentral.com)
  • These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. (umbc.edu)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
Intracellular tyrosine kinase1
  • Unique in the approach to abolishing function of this gene coded receptor, it was the first target of new monoclonal antibody therapy targeting the extracellular receptor and now also a target of small molecule drugs against the intracellular tyrosine kinase domain. (degruyter.com)
Epidermal growth14
Cell proliferation5
Dimerization3
Proteins4
  • The Bcl-2 family consists of a number of evolutionarily-conserved proteins that share Bcl-2 homology (BH) domains. (cancer-research-network.com)
  • Generally, these receptors explain their function on the cell membrane where, after the binding with growth factors or neuregulin undergo to homo or hetero oligomerization with the activation of the intrinsic tyrosine kinase activity and the subsequent recruitment of proteins involved in the cytoplasmic signalling pathways. (biomedcentral.com)
  • The EGFR proteins are receptor tyr kinases (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. (umbc.edu)
  • The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. (bioss.com.cn)
Pathway2
  • Activation of EGFR triggers activation of the ERK-signaling pathway in normal gastric epithelial and colon cancer cell lines. (signalchem.com)
  • Figure 4: Lrig1 controls endogenous signalling through the ErbB pathway. (nature.com)
Autophosphorylation1
  • Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation. (bioss.com.cn)
Antibody11
  • The Y877 kit contains phospho-ErbB-2 antibody that recognizes ErbB-2 only when phosphorylated at Tyr877, while the Y1248 kit provides a phospho-antibody that recognizes ErbB-2 only when phosphorylated at Tyr1248. (activemotif.com)
  • Non-transfected (-) and transfected (+) A431 whole cell extracts (15 μg) were separated by 5% SDS-PAGE, and the membrane was blotted with EGFR antibody [GT133] (GTX628887) diluted at 1:8000. (genetex.com)
  • Various whole cell extracts (30 μg) were separated by 5% SDS-PAGE, and the membranes were blotted with EGFR antibody [GT133] (GTX628887) diluted at 1:5000 and competitor's antibody diluted at 1:5000. (genetex.com)
  • Various whole cell extracts (30 μg) were separated by 5% SDS-PAGE, and the membrane was blotted with EGFR antibody [GT133] (GTX628887) diluted at 1:10000. (genetex.com)
  • The following product was used in this experiment: Phospho-EGFR (Tyr1068) Monoclonal Antibody (EP38Y) from Thermo Fisher Scientific, catalog # MA5-14485, RRID AB_10977041. (thermofisher.com)
  • CDC-Enhanced Tomuzotuximab is a Fc-modified anti-EGFR therapeutic biobetter antibody. (creative-biolabs.com)
  • Recombinant monoclonal antibody to EGFR. (creative-biolabs.com)
  • The antibody solution should be stored undiluted between 2°C and 8°C. Do not freeze . (biolegend.com)
  • To maximize performance, it is strongly recommended that the reagent be titrated for each application, and that you centrifuge the antibody dilution before adding to the cells at 14,000xg at 2 - 8°C for 10 minutes. (biolegend.com)
  • Antibody with azide - store at 2 to 8°C. Antibody without azide - store at -20 to -80°C. Antibody is stable for 24 months. (neobiotechnologies.com)
  • The lyophilized antibody is stable at room temperature for at least one month and for greater than a year when kept at -20°C. When reconstituted in sterile pH 7.4 0.01M PBS or diluent of antibody the antibody is stable for at least two weeks at 2-4 °C. (bioss.com.cn)
RTKs6
  • Signal transduction by receptor tyrosine kinases (RTKs) involves complex ligand- and time-dependent changes in conformation and modification state. (nature.com)
  • High resolution structures are available for individual receptors dimers, but less is known about receptor clusters that form in plasma membranes composed of many different RTKs with the potential to interact. (nature.com)
  • We report the use of multiplexed super-resolution imaging (Exchange-PAINT) followed by mean-shift clustering and random forest analysis to measure the precise distributions of five receptor tyrosine kinases (RTKs) from the ErbB, IGF-1R and Met families in breast cancer cells. (nature.com)
  • Nuclear localized HER family receptor tyrosine kinases (RTKs) have been observed in primary tumor specimens and cancer cell lines for nearly two decades. (plos.org)
  • This family of RTKs has been highly implicated in the formation and progression of various cancers via aberrant overexpression, kinase activation, and mutation [1] , [2] . (plos.org)
  • While the classical membrane-bound functions of HER family RTKs have been extensively studied, accumulating data suggest that these receptors can be found in the cell's nucleus where they can function as co-transcriptional activators [4] , [5] . (plos.org)
Her37
  • The current study aimed to map the putative transactivation domains (TADs) of the HER3 receptor. (plos.org)
  • Results from these analyses demonstrated that the C-terminal domain of HER3 (CTD, amino acids distal to the tyrosine kinase domain) contained potent transactivation potential. (plos.org)
  • To understand how the B 1 and B 2 regions influenced the transcriptional functions of nuclear HER3, we performed cyclin D1 promoter-luciferase assays in which HER3 deleted of the B 1 and B 2 regions was severely hindered in regulating this promoter. (plos.org)
  • Brand TM, Iida M, Luthar N, Wleklinski MJ, Starr MM, Wheeler DL (2013) Mapping C-Terminal Transactivation Domains of the Nuclear HER Family Receptor Tyrosine Kinase HER3. (plos.org)
  • Transphosphorylation of kinase-dead HER3 and breast cancer progression: a new standpoint or an old concept revisited? (biomedcentral.com)
  • Because kinase-inactive HER3 is not presently an amenable target for forthcoming HER TKIs, molecular approaches that can efficiently block heregulin-triggered HER3 transactivation or nucleocytoplasmic trafficking of heregulin might offer novel strategies with which to manage HER-driven breast cancer disease. (biomedcentral.com)
  • HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. (umbc.edu)
Tumors7
  • Amplification of the ErbB-2 gene and overexpression of its product has been detected in almost 40% of primary human breast tumors, which correlates with poor prognosis in node positive breast cancer. (activemotif.com)
  • ErbB-1 and ErbB-2 are found in many human cancers, and their excessive signaling may be critical factors in the development and malignancy of these tumors. (wikipedia.org)
  • Defective signaling of EGFR and other receptor tyrosine kinases in humans has been linked to diseases such as Alzheimer's disease, while overexpression has been linked to the development of various tumors. (promab.com)
  • Increased production or activation of EGFR has been associated with poor prognosis in a variety of tumors. (thermofisher.com)
  • Targeted molecular therapy against EGFR has shown promise as an adjuvant therapy in preliminary studies in several solid tumors, including head and neck cancer. (medscape.com)
  • An important development in cancer research over the past 2 decades has been the recognition that genetic changes drive the pathogenesis of tumors of both adulthood and childhood. (medscape.com)
  • [ 2 ] Targeted disruption of TP53 in the mouse leads to the development of various tumors (see image below). (medscape.com)
ErbB41
  • Another isoform lacks the phosphoinositide 3-kinase activation sequence present in the ErbB4 cytoplasmic domain. (rndsystems.com)
Glycoprotein2
  • EGFR is the receptor for members of the EGF family and is a transmembrane glycoprotein that has tyrosine kinase activity. (signalchem.com)
  • Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit. (wikidata.org)
Single transmembrane1
  • Receptors of this family are located on the plasma membrane and consist of an extracellular ligand-binding domain that is connected to a large intracellular domain by a single transmembrane sequence. (neobiotechnologies.com)
Signal transduction1
  • These receptors convert signals received from the extracellular environment into cell decisions such as growth and survival C a process termed signal transduction. (researchhunt.com)
Anti-EGFR4
  • This product is designed as a tool for the delivery and expression of anti-EGFR CAR mRNA for research. (promab.com)
  • The product leverages the lipid nanoparticle (LNP) technology platform for simple and efficient delivery of anti-EGFR CAR mRNA to a variety of mammalian cells in vitro and in vivo. (promab.com)
  • The anti-EGFR CAR in this product is approximately 56 kD and consists of anti-EGFR scFv (single-chain variable fragment) linked to a second-generation CAR (chimeric antigen receptor) containing the CD8 hinge and transmembrane domain and 4-1BB and CD3ζ signaling domains. (promab.com)
  • The full-length amino acid sequence of this anti-EGFR CAR mRNA-LNP product is available upon request. (promab.com)
Mutations4
  • In many cancer types, mutations affecting EGFR expression or activity could result in cancer. (guwahatimail.in)
  • Preclinical and clinical studies have demonstrated that many of these mutations are transforming and sensitive to FDA-approved ERBB targeted therapies, including trastuzumab, ado-trastuzumab emtansine, lapatinib, and pertuzumab. (cornell.edu)
  • Computational analysis of the genetic variants revealed a reduction in the stabilization of the EGFR tethered form for both V550M and the common R521K variant with low energetic state (− ∆∆G). Molecular interactions analysis suggested that these mutations might affect the receptor's function and promote tumorigenesis. (biomedcentral.com)
  • Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. (umbc.edu)
Oncogene5
  • The ErbB-2 proto-oncogene, also called Neu, EGFR-2 or HER-2, is a member of the transmembrane receptor tyrosine kinase family, which also includes EGF receptor and EGFR-3 (HER-3 or ErbB-3). (activemotif.com)
  • The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. (wikipedia.org)
  • The amplification of the HER-2 oncogene occurs in ~25% of breast cancer patients and is associated with diminished disease-free and overall survival. (touchoncology.com)
  • ERBB is abbreviated from erythroblastic oncogene B, a gene isolated from avian genome. (iiab.me)
  • ErbB-2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFR. (iiab.me)
Epithelial3
  • EGFR is involved in epithelial tissue development and homeostasis. (genetex.com)
  • EphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. (oncotarget.com)
  • EGFR is expressed by epithelial and endothelial cells and is frequently expressed by epithelial carcinomas. (biolegend.com)
Cancers2
  • Upregulation or abnormal activation of EGFR is frequently found in glioblastomas, lung cancers, and breast cancers, among others. (genetex.com)
  • Activation of EGFR triggers mitogenic signaling in gastrointestinal mucosa, and its expression is upregulated in colon cancers and most neoplasms (2). (signalchem.com)
Consists1
  • The ErbB family consists of four plasma membrane-bound receptor tyrosine kinases. (iiab.me)
Binds1
  • Our lab has recently developed a new strategy to regulate RTK activity by designing a peptide that specifically binds to the transmembrane (TM) region of the RTK to allosterically modify kinase activity. (bvsalud.org)
Metastatic2
  • The use of trastuzumab when given with chemotherapy improves response rates and progression-free and overall survival of patients with HER-2-positive metastatic breast cancer. (touchoncology.com)
  • It soon became clear that patients with HER-2-overexpressing metastatic breast cancer were at high risk of developing CNS involvement. (touchoncology.com)
Amplification1
  • Loss of heterozigosity (LOH) EGFR overexpression/amplification and cyclooxygenase-2 (COX2) dysregulation in pre-malignant lesions have been associated with … The EGFR has been implicated in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. (ecolowood.com)
Therapies1
  • The purpose of this review is to discuss the importance of EGFR in oral pre-malignant lesions and the possible role of EGFR-targeted therapies for head and neck cancer chemoprevention. (ecolowood.com)
MAPK3
  • Activation of the tyrosine kinase domain leads to the activation of the whole range of downstream signaling pathways like PLCγ, ERK 1/2, p38 MAPK, PI3-K/Akt and more with the cell. (wikipedia.org)
  • Furthermore, molecular alterations of the EGFR activate pro-oncogenic signaling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR [ 5 ]. (biomedcentral.com)
  • inhibits EGFR-dependent activation of MAPK/ERK. (bioss.com.cn)
Molecular1
  • Network pharmacology analysis and molecular docking analysis jointly revealed that umbelliferone and scopoletin act on multiple targets, mostly tyrosine kinases, in combating RA. (frontiersin.org)
Regulates1
  • regulates EGFR degradation through TCEB1- and TCEB2-mediated ubiquitination and proteasomal degradation. (bioss.com.cn)
Poor prognosis1
  • Since the EGFR signalling promotes proliferation in tumor the EGFR receptors often represent a marker of resistance with poor prognosis. (biomedcentral.com)
Cancer9
  • Because of this, ErbB-2 is one of the major drug targets for breast cancer and other cancer treatments. (activemotif.com)
  • The HER/ErbB family of receptor tyrosine kinases drives critical responses in normal physiology and cancer, and the expression levels of the various HER receptors are critical determinants of clinical outcomes. (researchhunt.com)
  • Author Summary A family of cell surface molecules called the HER receptor family plays important roles in normal physiology and cancer. (researchhunt.com)
  • The HER receptor expression profile is a critical determinant of cell behavior [6], [7], and outcomes in cancer pathology. (researchhunt.com)
  • EGFR-targeted agents for treatment of HNSCC Pharmacologic strategies targeting the EGFR that have been approved for cancer therapy include. (ecolowood.com)
  • 2. Kobayashi S, et al: EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. (signalchem.com)
  • non-canonical EGFR-Met interactions are implicated in resistance to anti-cancer drugs but have not been previously detected in drug-naïve cells. (nature.com)
  • HER-2 is over-expressed in approximately 7-34% of patients with gastric cancer [20] [21] and in 30% of salivary duct carcinomas. (iiab.me)
  • We detected seven new EGFR genetic variants in 168 cancer patients and 114 controls. (biomedcentral.com)
Humans1
  • Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease, while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. (wikipedia.org)
Tumor cell1
  • The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. (medscape.com)
Domain7
  • It is a complex process due to the domain specificity and nature of the members of ErbB family. (wikipedia.org)
  • For the activation of kinase domain in the ErbB dimer, asymmetric kinase domain dimer of the two monomers is required with the intact asymmetric (N-C lobe) interface at the site of adjoining monomers. (wikipedia.org)
  • lacks kinase domain), and erbB-4. (iiab.me)
  • All four contain an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain that can interact with a multitude of signaling molecules and exhibit both ligand-dependent and ligand-independent activity. (iiab.me)
  • EGF receptor is concomitant to domains rearrangement in a way that domain I and III are accessible for EGF and when domain II dimerizes with another EGFR unfolded tethered form that rotated 90° on its vertical axis. (biomedcentral.com)
  • Current therapeutics target EGFR's kinase domain or extracellular region. (bvsalud.org)
  • We propose that the PET1-induced disruption of native TM interactions disturbs the conformation of the kinase domain in such a way that it inhibits EGFR's ability to send migratory cell signals. (bvsalud.org)