• Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. (genome.jp)
  • HER2 positive breast cancer is identified by the overexpression of human epidermal growth factor receptor-2 (HER2) protein in tumor tissue and results in an increased rate of cell proliferation. (her2support.org)
  • 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)
  • Renal epidermal growth factor receptor (EGFR) signaling is activated in models of diabetic nephropathy (DN), and inhibition of the EGFR signaling pathway protects against the development of DN. (diabetesjournals.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)
  • 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)
  • ErbB2, also called Neu and Her2 (human epidermal growth factor receptor 2), is a type I membrane glycoprotein that is a member of the ErbB family of tyrosine kinase receptors. (kactusbio.com)
  • ErbB family members serve as receptors for the epidermal growth factor (EGF) family of growth factors.Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. (kactusbio.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)
  • 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)
  • 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)
  • 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)
  • The notion that breast cancer disease can be viewed as a biological process that is driven by overactive human epidermal growth factor receptor (HER)1/2 receptor tyrosine kinases (RTKs) has led to development of various anti-HER tyrosine kinase agents. (biomedcentral.com)
  • The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. (bmj.com)
  • Alterations in receptor tyrosine kinases (TKs), such as the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1, include overexpression, amplification or mutations. (bmj.com)
  • Novel therapeutic agents, in particular those that specifically target members of the human epidermal growth factor receptor (HER (ErbB1)) pathway, have shown encouraging therapeutic efficacy. (bmj.com)
  • Binding of epidermal growth factor to EGFR induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation, differentiation, motility, and cell survival (1). (signalchem.com)
  • 1. Wang K, et al: Epidermal growth factor receptor-deficient mice have delayed primary endochondral ossification because of defective osteoclast recruitment. (signalchem.com)
  • HER2 is a member of the epidermal growth factor receptor ( ErbB ) family of genes, which encode proteins that are cell surface-bound tyrosine kinase proteins. (cancer.gov)
  • 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)
  • HER-2 (ErbB2) is a 185-kDa transmembrane tyrosine kinase with extensive homology to the epidermal growth factor receptor (EGFR). (touchoncology.com)
  • This family, which includes epidermal growth factor receptor (EGFR), plays a pivotal role in normal cell growth, lineage determination, repair, and functional differentiation. (medscape.com)
  • Tyrosine kinases are mainly classified as receptor tyrosine kinases and non-receptor tyrosine kinases, including crucial members.Epidermal growth factor receptor (EGFR) belongs to the ERBB family of receptor tyrosine kinases along with three other closely related receptors, namely HER-2, HER-3 and HER-4. (frontiersin.org)
  • The epidermal growth factor receptor (EGFR) is among the most well-studied signaling pathways in cancer progression. (bio-biz-navi.com)
  • Introduction Epidermal development element receptor (EGFR) was the 1st discovered from the ErbB category of receptor tyrosine kinases with a total of four users: Erbb1/EGFR, ErbB2/Her2, ErbB3 and ErbB4. (bio-biz-navi.com)
  • Gene Ontology (GO) analysis indicated that these DEGs were significantly related to the positive regulation of epidermal growth factor-activated receptor activity, the positive regulation of the ERBB (erb-b2 receptor tyrosine kinase) signaling pathway, the differentiation of trophoblast giant cells, oxygen transport, immune-related pathways, and inflammation-related pathways. (ankylosingspondylitistreatmentreport.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)
  • 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)
  • HER2 is so named because it has a similar structure to human epidermal growth factor receptor, or HER1. (iiab.me)
  • Overexpression of the epidermal growth factor receptor (EGFR) associates with a range of cancers while downregulation of EGFR signalling can inhibit cancer growth. (biomedcentral.com)
  • Human epidermal receptor growth factor 2 ( HER2 , ERBB2 ) gene amplification occurs in about 15-20% of invasive breast cancers and is associated with biologically aggressive disease and poor overall survival in the absence of systemic therapy. (medscape.com)
  • Last, continuing HER2 blockade with trastuzumab in combination with several chemotherapeutic agents is preferable for subsequent lines of therapy, and the combinations of lapatinib [a dual kinase inhibitor that targets the intracellular domain of HER2 and epidermal growth factor receptor (EGFR)] with trastuzumab or capecitabine are reasonable treatment options for some patients. (medscape.com)
  • Neratinib is an investigational, orally administered, irreversible inhibitor of the ErbB1 (EGFR), ErbB2 (HER2) and ErbB4 (HER4) kinases. (her2support.org)
  • This approach has made significant headway in a number of cancers, such as breast and lung carcinoma, where alterations in the EGFR/ERBB pathways proved to be the main drivers that could be targeted with specific small molecules [ 11 , 12 ]. (biomedcentral.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)
  • EGFR belongs to the HER/ERbB family of proteins that includes three other receptor tyrosine kinases, ERbB2, ERbB3, ERbB4. (thermofisher.com)
  • Phosphorylation of EGFR at certain residues is also mediated by Src-non-receptor kinase. (thermofisher.com)
  • EGFR activation signals multiple downstream signaling cascades such as the Ras - ERK, PI3-K - Akt, Jak - STAT and PKC pathways that help in growth and proliferation of cells. (thermofisher.com)
  • 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)
  • 3 The development of molecular targeted therapies aimed at these molecular alterations has generated great optimism for the treatment of cancers such as NSCLC, and drugs targeting the EGFR tyrosine kinase domain are now available. (bmj.com)
  • EGFR is the receptor for members of the EGF family and is a transmembrane glycoprotein that has tyrosine kinase activity. (signalchem.com)
  • Activation of EGFR triggers mitogenic signaling in gastrointestinal mucosa, and its expression is upregulated in colon cancers and most neoplasms (2). (signalchem.com)
  • Activation of EGFR triggers activation of the ERK-signaling pathway in normal gastric epithelial and colon cancer cell lines. (signalchem.com)
  • 2. Kobayashi S, et al: EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. (signalchem.com)
  • 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)
  • C-erbB-2/HER-2 is a member of the EGFR family. (neobiotechnologies.com)
  • It has been proposed that oncogenes (EGFR (ERBB), MET) and tumor suppressors (PTEN, TP53) may also be capable of altering the vesicular release of tissue factor (TF) from cells [4-6]. (biomedres.us)
  • 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)
  • EGFR and HER-2, lead to autophosphorylation of the intracellular domain through tyrosine kinase activity and subsequent stimulation of downstream cascade that may result in proliferation, suppression of apoptosis, metastasis and angiogenesis. (frontiersin.org)
  • They have mainly been identified as important targets for several types of cancer such as EGFR for non-small-cell lung cancer, glioma and colorectal cancer, HER-2 for breast and colorectal cancers and Abl for chronic myeloid leukemia. (frontiersin.org)
  • Aberrant activity of tyrosine kinases, in particular EGFR and Abl, have been reported to induce apoptosis and cell cycle arrest in response to a wide range of stimuli resulting in neurodegeneration and neuroinflammation. (frontiersin.org)
  • 2 Since its finding, EGFR continues to be characterized like a mediator of a multitude of signal transduction occasions that control cell proliferation, migration and success. (bio-biz-navi.com)
  • 7 Another setting of EGFR activation in malignancy is usually activating somatic mutations that bring about constitutive kinase activity, and they are especially common in NSCLC (examined in Morgensztern examined the effectiveness of merging gefitinib with docetaxel in metastatic BC in comparison with docetaxel only. (bio-biz-navi.com)
  • Ligand binding induces EGFR dimerization and autophosphorylation, initiating the MAPK, Akt, and JNK signaling pathways. (biolegend.com)
  • ErbB-2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFR. (iiab.me)
  • This study determines the effects of krill oil extract on the migration of human CRC cells, and its potential role in modulating EGFR signalling pathway and the expression of programmed death ligand 1 (PD-L1). (biomedcentral.com)
  • The expression of EGFR, phosphorylated EGFR (pEGFR), protein kinase B (AKT), phosphorylated AKT (pAKT), extracellular signal regulated kinase (ERK1/2), phosphorylated ERK1/2 (pERK1/2) as well as PD-L1 were assessed by western blotting and immunohistochemistry. (biomedcentral.com)
  • The potential anti-cancer properties of krill oil are likely to be associated with the downregulation of EGFR, pEGFR and their downstream pERK/ERK1/2 and pAKT/AKT signalling pathways along with the downregulation of PD-L1. (biomedcentral.com)
  • Activating point mutations in ErbB/Her2 receptor tyrosine kinases have an infamous role in promoting oncogenesis across several different cancers, including breast and lung. (cancer.gov)
  • Inhibited HER2 activities include downstream signal transduction events and cell cycle regulatory pathways, such as the cell division cycle, ultimately resulting in decreased cell proliferation. (her2support.org)
  • The HER2 receptor does not bind to any known ligands, however, its dimerization arm is innately positioned in an open conformation. (plos.org)
  • The incorporation of markers such as HER3 transactivation, HER2/HER3 dimer, or others that may provide information regarding the level of HER pathway engagement has been demonstrated to allow identification of patients who respond to or escape HER-targeted therapies. (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)
  • 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)
  • HER2-positive (HER2+) breast cancers are defined as those that have an excess number of HER2 genes or over-produce the protein product of the HER2 gene, the HER2 cell surface receptor. (cancer.gov)
  • The ALTTO clinical trial was unique in that, for all of patients, there was central pathology review of the primary tumor, including re-evaluation of the cancer's estrogen receptor (ER), progesterone receptor (PR), and HER2 status, before patients were randomly assigned to one of the trial's four treatment groups. (cancer.gov)
  • About 15 percent to 20 percent of breast cancers are HER2-positive and about half of the HER-2 positive cancers also express ER and/or PR. (cancer.gov)
  • It is a tyrosine kinase inhibitor that enters a cancer cell and binds to the part of the HER2 protein that sits just beneath the cell's outer membrane. (cancer.gov)
  • Breast cancer tumors that do not express hormone receptors or have amplification of Her2/Neu (so called triple-negative tumors) have a poor prognosis and no validated molecular targets. (cancer.gov)
  • 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)
  • In fact, it not only yielded, in combination with chemotherapy, a significant improvement in progression-free and overall survivals, [ 2 ] but also allowed the evolution of the other HER2-targeted therapies, which currently represent the mainstay of treatment for locally advanced and metastatic breast cancer (mBC) with an HER2 amplification. (medscape.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)
  • 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)
  • 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)
  • Given that receptor tyrosine kinases of the ErbB family are overexpressed in a high proportion of metastatic bladder tumours, approaches involving small-molecule inhibitors of ErbB receptors in combination with conventional cytostatic drugs are of potential interest. (edu.kz)
  • 25 Furthermore to kinase inhibitors, medical tests have also examined the addition of the ligand obstructing monoclonal antibody cetuximab towards the DNA-alkylating agent carboplatin. (bio-biz-navi.com)
  • 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)
  • My results show that ErbB4 is expressed in BV-2, EOC-20 and RAW 264.7 cell lines while ErbB2-4 receptors are expressed in primary microglia. (uwaterloo.ca)
  • Heterodimer activation of the ErbB2/ErbB3 oncogenic unit induces cancer cell proliferation via PI3K/AKT signaling pathways. (cancer.gov)
  • ErbB2 belongs to the ErbB family of receptor tyrosine kinases, which has been implicated in a variety of human cancers , including cancers of the breast. (her2support.org)
  • We find that U87 mg electrotaxis is abolished under pharmacological inhibition of PI3Kγ, mTOR, AKT and ErbB2 signaling, whereas DAOY cell electrotaxis was not attenuated by these or other pathways evaluated. (nature.com)
  • 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)
  • Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. (neobiotechnologies.com)
  • The enhancement in metastatic properties was also found to occur via activation of ERBB2 receptor signaling pathways [2]. (biomedres.us)
  • Such effects were found to be mediated by PI3k/ Akt signaling pathways since the increased these ERBB2 sensitive coagulation proteins in a way that was commensurate with the activity of p-ERK and p-Akt. (biomedres.us)
  • The finding is the first time shown pro-tumour gene ERBB2 enable to modulate coagulation protein expression and clotting kinetics in breast cancer cells, it is via the PI3k/Akt pathways, which further supports the proposal that the state of the coagulation system in cancer is directly influenced by oncogenic transformation. (biomedres.us)
  • 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)
  • Canertinib (CI-1033, PD 183805) is a pan-erbB tyrosine kinase inhibitor. (lclabs.com)
  • Canertinib is an irreversible tyrosine kinase inhibitor. (lclabs.com)
  • Radiosensitization by pan ErbB inhibitor CI-1033 in vitro and in vivo. (lclabs.com)
  • Here, we show that the dual inhibitor of ErbB receptors, lapatinib, enhances cytostatic and induces cytotoxic effects of GTC in two bladder cancer cell lines which differ with regard to expression levels of proteins taking part in the ErbB pathway. (edu.kz)
  • These results showed that NRG is able to increase α7AChRs in microglia and macrophages after the phosphorylation of the ErbB4 receptors. (uwaterloo.ca)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. (genome.jp)
  • These include the adaptors Crk, Nck, the phospholipase C gamma (PLCgamma), the intracellular tyrosine kinase Src, or the Cbl E3 ubiquitin protein ligase. (genome.jp)
  • Protein glycosylation, the enzymatic process that attaches glycans or sugar molecules to proteins, plays a crucial role in cancer development processes, such as cell-cell adhesion, cell growth, ligand-receptor binding, and tumor metastasis. (cancer.gov)
  • 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)
  • Of the 31 genes, the 21 upregulated genes were primarily associated with cell paracrine and intracellular signaling, transcription regulation and cell adhesion and migration, and their transcriptional products included transforming growth factor-β2 (TGF-β2), insulin-like growth factor-binding protein 2 and transcriptional factor AP-2α/γ ( 11 ). (spandidos-publications.com)
  • 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)
  • The total-ErbB-2 antibody supplied in the FACE ErbB-2 Kits recognizes ErbB-2 protein regardless of its phosphorylation site. (activemotif.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)
  • Some of the new approaches depend on tumor biology and aim specifically to inhibit tumor growth and metastasis by targeting the tumor microenvironment or vasculature (leaving normal cells unaffected) or focusing on specific protein or signal transduction pathways. (medscape.com)
  • Cbl proteins belong to the RING finger class of ubiquitin protein ligases (E3s) and function as E3s for activated tyrosine kinases. (cancer.gov)
  • In addition to plexins, various other proteins have been implicated either as receptors for semaphorins or as components of the semaphorin receptor complex ( Pasterkamp and Kolodkin, 2003 ). (rupress.org)
  • Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. (genome.jp)
  • 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)
  • Its effect on the function of other proteins in the ErbB family of proteins that may also fuel cancer cell growth is being studied. (cancer.gov)
  • The effect of over expression on the synthesis and activities of selected blood coagulation proteins was determined as well as relevant signaling pathways. (biomedres.us)
  • 1) We study Cbl proteins, a family of ubiquitin ligases that negatively regulate signaling by receptor tyrosine kinases. (cancer.gov)
  • We are investigating the function of Cbl proteins, a family of proteins that regulate tyrosine kinase activity. (cancer.gov)
  • KEGG is an integrated database resource consisting of eighteen databases that are clustered into 4 main categories: 1) systems information (e.g. hierarchies and maps), 2) genomic information (e.g. genes and proteins), 3) chemical information (e.g. biochemical reactions), and 4) health information (e.g. human disease and drugs) https://www.kegg.jp/kegg/kegg1a.html . (univ-lyon1.fr)
  • We aimed to determine the signaling pathway regulating cell metabolism and the mechanism related to the regulation of human tumor-associated macrophages (TAMs) in gastric cancer (GC). (cancerindex.org)
  • In case you missed it, this final article (part 2 of 2) in the Investigator Spotlight Series, developed and written by Dr. Dawn Hayward, Office Clinical Cancer Proteomic Research (OCCPR) NCI Communications Fellow, highlights our up and coming Clinical Proteomic Tumor Analysis Consortium (CPTAC). (cancer.gov)
  • To further understand electrotactic migration of tumor cells, we performed RNA-sequencing for pathway discovery to identify signaling that is differentially affected by the exposure of direct-current electrical fields. (nature.com)
  • Persons with the most common pediatric brain malignancy, medulloblastoma, fare only slightly better than average, with a 71.9% 5-year survival, though the most common adult brain tumor, glioblastoma multiforme (GBM), incurs a mere 5.1% 5-year survival rate 2 . (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)
  • Membrane-bound HER receptors activate numerous tumor promoting signaling cascades via this mechanism, including the PI3K/AKT, Ras/Raf/Mek/Erk, PLCγ/PKC, and signal transducer and activator of transcription (STAT) pathways [1] , [2] . (plos.org)
  • However, they also may have limited effectiveness in some patients whose tumor growth depends on molecules that are not exclusively targeted by the agents or whose cancer mutates to use other growth pathways. (cancer.gov)
  • The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. (medscape.com)
  • On the other hand, c-Abl (Abl-1) is a non-receptor tyrosine kinase, which is also essential in the regulation of several antiapoptotic and proliferative signal transduction pathways. (frontiersin.org)
  • My laboratory studies signal transduction pathways that regulate growth and programmed cell death in epithelial cancer cells, with a focus on breast and ovarian cancer. (cancer.gov)
  • The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. (genome.jp)
  • 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)
  • 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)
  • Downstream signaling from these receptors proceeds TSPAN10 via tyrosine phosphorylation. (bio-biz-navi.com)
  • Dimerisation results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways. (iiab.me)
  • 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)
  • 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-2 overexpression is also observed in ovarian, gastric, salivary and non-small cell lung carcinomas. (activemotif.com)
  • 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)
  • These in vivo data suggest that the Gq-coupled 5-HT(2B)R uses the signaling pathway of the tyrosine kinase receptor ErbB-2 for cardiac differentiation. (hal.science)
  • Tyrosine kinases, which catalyze the transfer of a phosphate from ATP to a hydroxyl group of a tyrosine residue, play a plethora of roles in the regulation of diverse functions in normal cells including cell growth, motility, differentiation, and metabolism. (frontiersin.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • Involvement of C/EBPβ-related signaling pathway in methamphetamine-induced neuronal autophagy and apoptosis. (cancerindex.org)
  • Canertinib inhibited erbB receptor phosphorylation and induced growth inhibition and apoptosis at concentrations of 1 µM or more. (lclabs.com)
  • Alterations in gene sequence or expression can occur in the cell-signalling and regulatory pathways involved in cell-cycle control, apoptosis, proteosome regulation and angiogenesis. (bmj.com)
  • 2) We investigate induction of apoptosis in breast cancer cells by TRAIL receptor agonists. (cancer.gov)
  • In a second project we are investigating the induction of apoptosis by activation of death receptors for the ligand TRAIL in breast and ovarian cancer cells. (cancer.gov)
  • We have shown that most breast and ovarian cancer cell lines are resistant to the induction of apoptosis by TRAIL, the ligand for the death receptors DR4 and DR5. (cancer.gov)
  • We have demonstrated that resistance to TRAIL-induced apoptosis can be overcome by co-incubation of the cells with chemotherapeutic agents, semi-synthetic retinoids (such as 4HPR), or molecularly targeted agents (such as anti-ErbB-2 antibodies). (cancer.gov)
  • 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. (iiab.me)
  • 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)
  • 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)
  • It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family (IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g. (wikipedia.org)
  • Neuregulin signals through the ErbB receptors, a family of tyrosine kinase receptors, to facilitate the effects on ACh expression. (uwaterloo.ca)
  • Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. (rupress.org)
  • The erbB family of receptor tyrosine kinases plays critical roles in human cancers, including pancreatic cancer. (aacrjournals.org)
  • Discovering a specific agent, which targets multiple members of the erbB family, would be important in pancreatic cancer therapy. (aacrjournals.org)
  • Essential erbB family phosphorylation in osteosarcoma as a target for CI-1033 inhibition. (lclabs.com)
  • 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)
  • The ErbB family consists of four plasma membrane-bound receptor tyrosine kinases. (iiab.me)
  • EphB4 is a member of the largest family of receptor tyrosine kinases and is an important regulator of fundamental physiological and pathophysiological processes such as tissue patterning during development, angiogenesis and tumour progression [ 1 ]. (oncotarget.com)
  • 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)
  • Administration of kinase regulator Huaier ( Trametes robiniophila murr ) has been reported significantly effective on the broad range of cancers (Chinese administration license No. Z-20000109) [1-12]. (fortunejournals.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)
  • Human epithelial malignancies frequently display deregulated tyrosine kinase activity. (cancer.gov)
  • The prostaglandin-endoperoxide synthase 2 gene (PTGS2), which encodes cyclooxygenase-2, was found to upregulate the expression of TGF-β2 ( 14 ). (spandidos-publications.com)
  • Inactivation of the 5-HT(2B) receptor (5-HT(2B)R) gene leads to embryonic and neonatal death due to the following defects in the heart: (a) 5-HT(2B)R mutant embryos exhibit a lack of trabeculae in the heart and a reduction in the expression levels of a tyrosine kinase receptor, called ErbB-2, leading to mid-gestation lethality. (hal.science)
  • ERBB is abbreviated from erythroblastic oncogene B, a gene isolated from avian genome. (iiab.me)
  • Briefly, the user provides a KEGG formatted species id for either human, mouse or rat, and the package will download and store species specific ENTREZ gene IDs and map them to their respective KEGG pathways by accessing the KEGG REST API. (univ-lyon1.fr)
  • Next, the user will identify significantly enriched pathways in two different gene sets, and finally, the user will identify pathways that are differentially enriched between the two gene sets. (univ-lyon1.fr)
  • One key component of a statistically rigorous functional enrichment analysis is the definition of a background data set that can be used to estimate the number of candidate genes that are 'expected' to be associated with the pathway by chance, e.g., if 5% of genes in the background data set are associated with a pathway then 5% of candidate gene are expected to be associated with the pathway by chance. (univ-lyon1.fr)
  • Tyr is the phosphorylation site that is most tightly linked to oncogenic transformation and coupling to the ras/MAP kinase signaling pathway. (ihcworld.com)
  • Because of this, ErbB-2 is one of the major drug targets for breast cancer and other cancer treatments. (activemotif.com)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. (genome.jp)
  • The results revealed significant differences in the behavior and coordination of RNA editing events, biomolecules, and multiple signaling pathways which beyond any speculations from the findings in the process of carcinogenesis. (fortunejournals.com)
  • The DEGs were also closely related to the TNF and NF-κB signaling pathways. (ankylosingspondylitistreatmentreport.com)
  • EphB4 over-production promotes ligand-independent signaling pathways that increase cancer cell viability and stimulate migration and invasion. (oncotarget.com)
  • Epo-R, Tpo-R, GH-R, PRL-R). The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains (SH2/SH3) and the presence of up to seven JAK homology domains (JH1-JH7). (wikipedia.org)
  • Nonetheless the terminal JH domains retain a high level of homology to tyrosine kinase domains. (wikipedia.org)
  • Sample Kinase Activity Plot. (signalchem.com)
  • Within the project using next generation sequencing technology and signal transduction pathway activity profiling technology, we have identified novel pathways and biomarkers implicated in cervical carcinogenesis. (europa.eu)
  • Functional enrichment examines whether the number of genes in the list associated with a biological function or particular pathway is more than would be expected by chance. (univ-lyon1.fr)
  • As an example, enrichment of a particular pathway among a list of genes that are differentially expressed after an experimental manipulation may indicate that the pathway has been altered by that manipulation. (univ-lyon1.fr)
  • In a recent publication in the journal Clinical Chemistry, CPTAC investigators from Fred Hutchinson Cancer Research Center described a robust technique for evaluating biomarker expression of key receptors in patients with breast cancer bone metastasis using non-decalcified bone biopsies in immuno. (cancer.gov)
  • Patients harboring mutations in actionable pathways were more likely to succumb from recurrent disease compared with those who did not, suggesting that the former should be considered for treatment with targeted compounds in future trials. (biomedcentral.com)
  • The rate of lost markers was 1.2% (2 out of 164 MS). In 15 out of 151 patients (9.9%), MRI assessment was reported to be compromised by MS placement. (bvsalud.org)
  • 2) in AS patients and 329 were downregulated (FC (ankylosingspondylitistreatmentreport.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)
  • The correlation of the inflammatory profile with the severity of the disease in neoplastic patients with SARS-CoV-2 infection was addressed. (cdc.gov)
  • This mutation (V617F), a change of valine to phenylalanine at the 617 position, appears to render hematopoietic cells more sensitive to growth factors such as erythropoietin and thrombopoietin, because the receptors for these growth factors require JAK2 for signal transduction. (wikipedia.org)
  • Genetic mutation promotes biological evolution and results in biodiversity ( 2 , 3 ). (spandidos-publications.com)
  • It not only inhibits tyrosine phosphorylation but also enhances ubiquitinylation and accelerates endocytosis and subsequent intracellular destruction of ErbB-2 molecules. (lclabs.com)
  • In FACE, cells are cultured in 96-well plates and stimulated to induce the pathway of interest. (activemotif.com)
  • The FACE ErbB-2 (Y1248) and ErbB-2 (Y877) Kits were used to assay the levels of total and phosphorylated ErbB-2 contained within untreated or EGF treated A-431 cells. (activemotif.com)
  • Lapatinib inhibited phosphorylation of ErbB receptors and also reduced the level of phosphorylated AKT. (edu.kz)
  • In RT112 cells, which express high levels of ErbB receptors and harbour wild-type p53, combined GTC/lapatinib treatment resulted in the phosphorylation of p53 at Ser46 and accumulation of sub-G 1 cell populations. (edu.kz)
  • Huaier efficacy on the activation of Hedgehog signaling pathway was followed by the subsequent inhibition at 3-6 months interval. (fortunejournals.com)
  • 2 There is only limited knowledge of the factors that predict for the development of CNS metastasis, but the main ones reported include young age, African ethnicity, oestrogen receptor (OR)-negativity, HER 2 -positivity, high tumour grade and BRCA 1 phenotype. (touchoncology.com)
  • The molecular basis of hair growth was identified as the activation of Hedgehog signaling pathway, which initiates systematic tissue repair not only in cancer lesions together with the cure of skin problems and perturbed inter/ intra neural signal transfer. (fortunejournals.com)
  • Cancer Res (2006) 66 (2): 1025-1032. (aacrjournals.org)
  • We have identified anti-cancer effects of Huaier, and its unique characteristics of 1) no side effects or toxicity, 2) in dose dependent manner, 3) causing specific cancer cell death with simultaneous tissue regeneration, 4) miRNA-mediated transcriptional control on the rescue of multiple signal transduction, by dependent on individual genomic potential. (fortunejournals.com)
  • Recent advancement in technology enabled to cultivate those useful species in quantity, and quality-controlled distribution in the conventional granule forms has begun since 1970's, and currently Huaier is recognized widely as the patent anti-cancer drug in China (Chinese administration license No. Z-20000109) [2, 4, 5]. (fortunejournals.com)
  • Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy. (lclabs.com)
  • 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)
  • 2 The pathogenesis of lung cancer involves the accumulation of several molecular abnormalities over time. (bmj.com)
  • With the increased understanding of molecular mechanisms and basic pathways in the pathogenesis of squamous cell cancer of the head and neck , these pathways may be modified, and rational approaches in cancer therapy at the molecular level may be created. (medscape.com)
  • Understanding the mechanisms that regulate signaling by these kinases should uncover new ways to inhibit cancer cell growth. (cancer.gov)
  • 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)
  • Furthermore, diverse structural alterations have been identified that cause ligand-independent firing of this receptor, doing so in the absence of receptor over-expression. (iiab.me)
  • Importantly, these Notch pathway alterations were prognostic on multivariate analyses. (biomedcentral.com)
  • Canertinib alkylates a cysteine residue specific to ErbB receptors. (lclabs.com)
  • 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)