• as a cell surface-associated protein, it is easily accessible to drugs and as a kinase it is amenable to targeted inhibition by small molecules. (antibodyguide.com)
  • Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ERBB2 gene. (wikipedia.org)
  • lacks kinase domain), and erbB-4. (wikipedia.org)
  • Signaling pathways activated by HER2 include: mitogen-activated protein kinase (MAPK) phosphoinositide 3-kinase (PI3K/Akt) phospholipase C γ protein kinase C (PKC) Signal transducer and activator of transcription (STAT) In summary, signaling through the ErbB family of receptors promotes cell proliferation and opposes apoptosis, and therefore must be tightly regulated to prevent uncontrolled cell growth from occurring. (wikipedia.org)
  • Phosphorylation of EGFR at certain residues is also mediated by Src-non-receptor kinase. (thermofisher.com)
  • Receptor tyrosine-protein kinase erbB-2, also known as HER2/Neu (human epidermal growth factor receptor 2), is a member of the human epidermal growth factor receptor family. (meridianbioscience.com)
  • A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. (bvsalud.org)
  • Canertinib (CI-1033, PD 183805) is a pan-erbB tyrosine kinase inhibitor. (lclabs.com)
  • It selectively inhibits erbB1 (epidermal growth factor receptor), erbB2, erbB3, and erbB4 without blocking tyrosine kinase activity of many other receptors such as platelet-derived growth factor receptor, fibroblast growth factor receptor, and insulin receptor. (lclabs.com)
  • The degradative pathway of ErbB receptor tyrosine kinases stimulated by tyrosine kinase inhibitors appears to be chaperone mediated, and thus is similar to the pathways activated by the heat shock protein 90 (Hsp90) antagonist geldanamycin and by stress-induced mechanisms. (lclabs.com)
  • However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. (arigobio.com)
  • Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. (arigobio.com)
  • Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been emerged as the standard selection in non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutations. (biomedcentral.com)
  • Owing to the well-established beneficial outcomes of clinical trials, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), have been approved as the standard regimens in patients with non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations [ 1 ]. (biomedcentral.com)
  • Osimertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) at approximately 9-fold lower concentrations than wild-type. (drugcentral.org)
  • c- erb B-2 (HER-2/ neu ) is a 185 kDa receptor tyrosine kinase belonging to the epidermal growth factor receptor family, which also includes EGFR (HER-1), c- erb B-3 (HER-3), and c- erb B-4 (HER-4). (ihcworld.com)
  • HER2 is certainly a CAY10471 Racemate known person in the ErbB/HER receptor tyrosine kinase family members1,2,3. (president2010.info)
  • HER2 BC cells using a 3+ immunohistochemistry (IHC) rating display high basal degrees of receptor kinase activity and phosphorylation, and these induce CAY10471 Racemate constitutive activation from the mitogen-activated proteins phosphatidylinositol and kinase 3-kinase/Akt pathways8. (president2010.info)
  • Proteins used in this study are Mucin-4, Phosphatase And Tensin Homolog, and Receptor tyrosine-protein kinase erbB-2. (ui.ac.id)
  • Antibody-drug conjugates targeting receptor tyrosine-protein kinase erbB-2 ( ERBB2, HER2 ) have emerged as promising targeted options for HER2 -mutant NSCLC. (egfrcancer.org)
  • Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. (rupress.org)
  • Binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of ErbB-2, resulting in the phosphorylation of both plexin-B1 and ErbB-2. (rupress.org)
  • Like sorafenib, lapatinib is a protein kinase inhibitor shown to decrease tumor-causing breast cancer stem cells. (hmdb.ca)
  • 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)
  • 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)
  • ERBB2 is a protein that is also known as HER2 (human epidermal growth factor receptor 2). (antibodyguide.com)
  • It is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. (antibodyguide.com)
  • Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. (nih.gov)
  • The human protein is also frequently referred to as HER2 (human epidermal growth factor receptor 2) or CD340 (cluster of differentiation 340). (wikipedia.org)
  • HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. (wikipedia.org)
  • HER2 is so named because it has a similar structure to human epidermal growth factor receptor, or HER1. (wikipedia.org)
  • Expression analyses of epidermal growth factor receptor and HER-2/neu: no advantage of prediction of recurrence or survival in breast cancer patients. (thieme-connect.de)
  • MA5-14485 targets Epidermal Growth Factor Receptor in IHC (P) applications and shows reactivity with Human samples. (thermofisher.com)
  • EGFR (Epidermal growth factor receptor, HER1, ErbB1) is encoded by the EGFR gene located on chromosome 7 in humans. (thermofisher.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)
  • Recently, we isolated a novel negative regulator of epidermal growth factor receptor (EGFR), termed EGFR-related protein (ERRP), whose expression attenuates EGFR activation. (aacrjournals.org)
  • Patients with breast cancer positive for human epidermal growth-factor receptor type 2 (HER2) are an important subgroup for consideration in the Asian context. (mcmaster.ca)
  • 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)
  • This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. (arigobio.com)
  • Lymph node, epidermal growth factor receptor, and estrogen receptor status, tumor size, and histological grade also had prognostic significance but, applying multivariate analysis, only lymph node status was a more important predictor of relapse-free and overall survival than staining for the oncoprotein. (ox.ac.uk)
  • Positive staining was correlated with negative estrogen receptor status and high histological grade, but there was no association with either lymph node or epidermal growth factor receptor status or tumor size. (ox.ac.uk)
  • In our prior research of epidermal development aspect receptor (EGFR) dimerization dynamics at a single-molecule level, we demonstrated that receptor activation by ligand binding is certainly spatially asymmetric on cells overexpressing EGFR (ref. 13). (president2010.info)
  • Regulation of cyclooxygenase-2 by interferon γ and transforming growth factor α in normal human epidermal keratinocytes and squamous carcinoma cells. (houstonmethodist.org)
  • While traditional, routinely measured biomarkers such as estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2) still represent the best prognostic and predictive biomarkers for HR+ breast cancer, a significant proportion of patients either do not respond to endocrine therapy or develop endocrine resistant disease. (ox.ac.uk)
  • But contrary to other members of the ERBB family, HER2 does not directly bind ligand. (wikipedia.org)
  • HER2 activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high, for instance in cancer. (wikipedia.org)
  • Molecular cloning of the gene showed that HER2, Neu, and ErbB-2 are all encoded by the same orthologs. (wikipedia.org)
  • HER2 can heterodimerise with any of the other three receptors and is considered to be the preferred dimerisation partner of the other ErbB receptors. (wikipedia.org)
  • HER2 proteins have been shown to form clusters in cell membranes that may play a role in tumorigenesis. (wikipedia.org)
  • Patients with a strong overexpression of the HER2 protein (IHC3+) specifically benefited from the treatment, with a median overall survival of 17.9 mo. (wjgnet.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)
  • This membrane deformation will not need receptor signalling actions, but outcomes from the high degrees of HER2 in the cell surface area. (president2010.info)
  • These features of HER2 overexpression had been acquired from several ensemble experiments, where receptor actions are averaged more than an extremely large numbers of cells typically. (president2010.info)
  • A lot of area points of specific HER2s had been obtained by monitoring one receptors (for 100?s in a 10.72?Hz acquisition price) labelled with anti-HER2 Fab:QD (H2Fab:QD) conjugates using total inner reflection fluorescence microscopy (TIRFM)13. (president2010.info)
  • We initial likened the receptor distribution patterns inside the same cell type where HER2 appearance levels had been artificially changed. (president2010.info)
  • EGFR belongs to the HER/ERbB family of proteins that includes three other receptor tyrosine kinases, ERbB2, ERbB3, ERbB4. (thermofisher.com)
  • In both MYC and ERBB2 amplified tumour cells, ibrutinib downregulated ERK-mediated signal transduction, cMYC Ser-62 phosphorylation and levels of MYC protein, and elicited G1 cell cycle arrest and apoptosis, suggesting that this drug could be used to treat biomarker-selected groups of patients with oesophageal cancer. (icr.ac.uk)
  • 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)
  • ErbB-2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFR. (wikipedia.org)
  • Phosphorylation of EGFR at Y1086 specifically allows binding of the adaptor protein GRB2, leading to activation of the MAPK pathway. (thermofisher.com)
  • Upon receptor activation and signaling, EGFR is endocytosed and targeted for degradation or recycling. (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)
  • In the current study, we examined the effects of recombinant ERRP on the growth and ligand-induced activation of multiple members of erbB family in three pancreatic cancer cell lines that express varying levels of EGFR and other member(s) of its family, specifically HER-2. (aacrjournals.org)
  • ERRP also inhibited ligand-induced activation of EGFR, HER-2, and HER-3 (ErbB3). (aacrjournals.org)
  • In contrast, Erbitux and Herceptin only partially or modestly inhibited activation of EGFR, HER-2, and HER-3. (aacrjournals.org)
  • 5 Beckmann M W, Niederacher D, Schnurch H G, Bender H G. The erbB gene family: significance for tumor development, prognosis and new therapeutic modalities. (thieme-connect.de)
  • The immunoreactivity of labeled proteins was preserved as confirmed by in vitro and in vivo binding to tumor cells. (duke.edu)
  • We tested possible down-modulating effects of these monoclonal antibodies on SKBR-3 mammary tumor cells, which express high levels of wild-type human neu protein. (prinsesmaximacentrum.nl)
  • Amplification of the HER-2 gene with overexpression of the protein occurs in 20-30% of breast cancers, and tumor progression in mammary cancer is associated with elevated levels of tyrosine-phosphorylated neu and erbB-3. (ihcworld.com)
  • [ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • Discovering a specific agent, which targets multiple members of the erbB family, would be important in pancreatic cancer therapy. (aacrjournals.org)
  • The HER-2/neu onkogene may play a role in the prognosis and management of patients with breast cancer. (thieme-connect.de)
  • Prospective studies correlating HER-2/neu overexpression with prognosis might provide additional data. (thieme-connect.de)
  • Expression of the c-erbB-2 oncoprotein appears to be an important independent indicator of prognosis in human breast cancer. (ox.ac.uk)
  • 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)
  • 32 % of patients exhibited overexpression of HER-2/neu. (thieme-connect.de)
  • c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes. (thieme-connect.de)
  • Gene amplification and overexpression of the proteins in breast malignancies (BCs) anticipate poor disease final result due to raised metastatic potentials4,5,6,7. (president2010.info)
  • ErbB-2 overexpression is also observed in ovarian, gastric, salivary and non-small cell lung carcinomas. (activemotif.com)
  • Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth. (arigobio.com)
  • Sensitivity of HER-2/neu antibodies in archival tissue samples of invasive breast carcinomas. (thieme-connect.de)
  • We have obtained monoclonal antibodies to the human neu protein by immunizing a Balb/c mouse with a Balb/c cell line expressing the human neu gene by transfection. (prinsesmaximacentrum.nl)
  • The monoclonal antibodies reacted with neu protein on intact cells by immunofluorescence and immunoprecipitated neu in metabolically labeled cells, also in the presence of tunicamycin. (prinsesmaximacentrum.nl)
  • In contrast, the antibodies induced 50-65% down-modulation in NIH3T3 cells expressing the mutated human neu protein and could inhibit these cells to form colonies in soft agar. (prinsesmaximacentrum.nl)
  • Each FACE ErbB-2 Kit provides 96 rxns each of 2 antibodies that enable you to monitor and compare the levels of both phosphorylated and total ErbB-2. (activemotif.com)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • Furthermore, diverse structural alterations have been identified that cause ligand-independent firing of this receptor, doing so in the absence of receptor over-expression. (wikipedia.org)
  • This finding could indicate that HER-2/neu expression is a new independent prognostic factor. (thieme-connect.de)
  • 2 Barnes D M, Lammie G A, Millis R R, Gullick W L, Allen D S, Altman D G. An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma. (thieme-connect.de)
  • Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer. (ox.ac.uk)
  • Expression of c-erbB-2 protein product in bladder cancer. (ox.ac.uk)
  • Cellular components and processes associated with DD pathogenesis include altered gene and protein expression of cytokines, growth factors, adhesion molecules, and extracellular matrix components. (biomedcentral.com)
  • BT-474 cells, obtained expression of the receptor has important implications for their biology from American Type Culture Collection, were maintained in RPMI 1640 and therapy (1). (lu.se)
  • Radiosensitization by pan ErbB inhibitor CI-1033 in vitro and in vivo. (lclabs.com)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • It not only inhibits tyrosine phosphorylation but also enhances ubiquitinylation and accelerates endocytosis and subsequent intracellular destruction of ErbB-2 molecules. (lclabs.com)
  • Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor. (univ-amu.fr)
  • Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member. (bvsalud.org)
  • Activation of HER-2 is frequent in ductal carcinoma in situ suggesting that HER-2 signaling plays a critical role in the early stages of breast tumorigenesis. (ihcworld.com)
  • Therefore, we utilized quantum dot (QD)-structured single-receptor monitoring and analysis strategies in live cells to research whether a spatial control exists that may impact the activation of overexpressed HER2s in BC cells. (president2010.info)
  • A dominant-negative form of ErbB-2 blocks Sema4D-induced RhoA activation as well as axonal growth cone collapse in primary hippocampal neurons. (rupress.org)
  • Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2-mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse. (rupress.org)
  • Following stimulation, the cells are fixed rapidly, which preserves activation-specific protein modifications. (activemotif.com)
  • Dimerisation results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways. (wikipedia.org)
  • Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (Probable). (arigobio.com)
  • ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. (wikipedia.org)
  • Systemic treatment of hormone receptor-positive (HR+) breast cancer is undergoing a renaissance, with a number of targeted therapies including CDK4/6, mTOR, and PI3K inhibitors now approved for use in combination with endocrine therapies. (ox.ac.uk)
  • The ErbB family consists of four individual plasma membrane-bound receptor tyrosine kinases. (wikipedia.org)
  • The erbB family of receptor tyrosine kinases plays critical roles in human cancers, including pancreatic cancer. (aacrjournals.org)
  • Essential erbB family phosphorylation in osteosarcoma as a target for CI-1033 inhibition. (lclabs.com)
  • Canertinib inhibited erbB receptor phosphorylation and induced growth inhibition and apoptosis at concentrations of 1 µM or more. (lclabs.com)
  • A database to provide information about the known and explored therapeutic protein and nucleic acid targets, the targeted disease, pathway information and the corresponding drugs directed at each of these targets. (idrblab.net)
  • [ 1 , 2 ] Although the chief target of the autoimmune attack in most cases is the skeletal muscle nicotinic acetylcholine receptor (nAChR), other antigenic targets that are components of the neuromuscular junction (NMJ) have also been implicated. (medscape.com)
  • Because of this, ErbB-2 is one of the major drug targets for breast cancer and other cancer treatments. (activemotif.com)
  • Her-2/neu is an oncogene, which is a type of gene that can contribute to certain types of cancer. (medic8.com)
  • 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 protein has no ligand binding domain of its own and therefore cannot bind growth factors. (arigobio.com)
  • The autoimmune attack occurs when autoantibodies form against the nicotinic acetylcholine postsynaptic receptors at the neuromuscular junction of skeletal muscles (see the image below). (medscape.com)
  • Normal neuromuscular junction showing a presynaptic terminal with a motor nerve ending in an enlargement (bouton terminale): Synaptic cleft and postsynaptic membrane with multiple folds and embedded with several acetylcholine receptors. (medscape.com)
  • Cases of invasive breast carcinoma with the phosphorylated receptor have displayed aggressive clinicopathological features and adverse prognoses. (ihcworld.com)
  • 14 King C R, Kraus M H, Aaronson S A. Amplification of a novel v-erbB-related gene in a human mammary carcinoma. (thieme-connect.de)
  • We also used NIH3T3 cells transfected with either a normal or a mutated human neu gene, encoding a protein with a valine to glutamic acid substitution in the transmembrane domain. (prinsesmaximacentrum.nl)
  • HER-2/neu amplification predicts poor survival in node-positive breast cancer. (thieme-connect.de)
  • Staining was performed using our Staining Membrane-associated Proteins protocol. (rndsystems.com)
  • We find that these receptors are intermixed nonhomogenously on the plasma membrane. (nature.com)
  • Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network. (univ-amu.fr)
  • Fast Activated Cell-based ELISA (FACE™) Kits provide a simple, sensitive method for detecting protein phosphorylation directly in the cell, without making extracts or performing electrophoresis and membrane blotting. (activemotif.com)
  • Purification: This antibody is purified through a protein A column, followed by peptide affinity purification. (hatinhibitor.com)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • This Part 2 post is concerned with anti-cancer drug and other interventions that simultaneously address multiple growth pathways. (anti-agingfirewalls.com)
  • We did the randomisation via an interactive response system under a permuted block randomisation scheme (block size of four), stratified by hormone receptor status, stage at diagnosis, and geographical location. (nih.gov)
  • Molecular Biomarkers for Contemporary Therapies in Hormone Receptor-Positive Breast Cancer. (ox.ac.uk)