Erbb 2 transmembrane tyrosine receptors receptor erbb 2. Medical search. Frequent questions

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)
The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. (wikipedia.org)
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)
HER-2 (ErbB2) is a 185-kDa transmembrane tyrosine kinase with extensive homology to the epidermal growth factor receptor (EGFR). (touchoncology.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)
The epidermal growth factor receptor (EGFR) continues to be implicated in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. (ecolowood.com)
Once activated these pathways contribute to the development of a malignant cellular phenotype including resistance to apoptosis increased proliferation invasion metastasis and stimulation of angiogenesis (Figure 1).1 Figure 1 Epidermal growth factor receptor (EGFR) pathway activation during HNSCC carcinogenic process. (ecolowood.com)
The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). (guwahatimail.in)
ErbB4, also called Her4 (human epidermal growth factor receptor 4), is a type I membrane glycoprotein that is a member of the ErbB family of tyrosine kinase receptors. (rndsystems.com)
Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. (nature.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)
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 human epidermal growth factor receptor 2 (HER2) status is important in the medical management of patients with various human cancers. (ijmpo.org)

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)
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)
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)
The ErbB family consists of four plasma membrane-bound receptor tyrosine kinases. (iiab.me)
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)
The leucine-rich repeat protein LRIG1 is a negative regulator of ErbB family receptor tyrosine kinases. (nature.com)
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)
Taken together, our present study identified umbelliferone and scopoletin as two major anti-rheumatic components from SL that may bind and inhibit tyrosine kinases and subsequently inactivate NF-κB in RA-FLSs. (frontiersin.org)
The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. (medscape.com)
Signal transduction by receptor tyrosine kinases (RTKs) involves complex ligand- and time-dependent changes in conformation and modification state. (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)
Unfortunately, following much clinical and basic science research, we have learned that simple measurement of overactive HER tyrosine kinases does not predict HER TKI efficacy. (biomedcentral.com)
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)

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)
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)
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)
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)
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)
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)
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)
The proto-oncogene designated erbB2 or HER2 encodes a 185-kilodalton transmembrane tyrosine kinase (p185erbB2), whose overexpression has been correlated with a poor prognosis in several human malignancies. (embl.de)

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)
Each kit contains a total-ErbB-2 antibody that recognizes ErbB-2 regardless of its phosphorylation state. (activemotif.com)
The total-ErbB-2 antibody supplied in the FACE ErbB-2 Kits recognizes ErbB-2 protein regardless of its phosphorylation site. (activemotif.com)
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)
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 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)
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)
ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase (PubMed:20682778). (univ-amu.fr)

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)
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)
HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands. (guwahatimail.in)
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)
The final cleavage is performed by -secretase, whose substrates include all four Notch receptors and their ligands as well as -amyloid precursor protein, E-cadherin, CD44, ErbB-4, and ephrin-B1 [2-8]. (scienceexhibitions.org)
Tumor cell nuclear expulsion results in an extracellular DNA-protein complex that is enriched with receptor for advanced glycation endproducts (RAGE) ligands. (bvsalud.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)

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)

Dimerisation results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways. (iiab.me)
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)
It first binds with high affinity to specific cell-surface receptors and then induces their dimerization, which is essential for activating the tyrosine kinase in the receptor cytoplasmic domain, initiating a signal transduction that results in DNA synthesis and cell proliferation. (embl.de)

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)
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)

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)

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)
Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. (wikipedia.org)
The chromatin-bound RAGE ligand S100a4 activates RAGE receptors in neighboring surviving tumor cells, leading to Erk activation. (bvsalud.org)

ErbB protein family signaling is important for development. (wikipedia.org)
Mucin-4 may play a role in regulating cellular adhesion and in cell surface signaling from the ERBB-2 RECEPTOR PROTEIN-TYROSINE KINASE. (uams.edu)
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)
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)
The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. (cancerindex.org)
Introduction Notch is a family of single-pass type I transmembrane protein receptors that, in mammals, includes four homologs, Notch1 to 4 [1]. (scienceexhibitions.org)
Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. (univ-amu.fr)

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)
ErbB-2 was named for its similarity to ErbB (avian erythroblastosis oncogene B), the oncogene later found to code for EGFR. (iiab.me)
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)
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)
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)

Typically, heterodimerization with ErbB2 forms the high affinity receptor complex. (rndsystems.com)

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)
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)
Ligand-induced Notch receptor activation requires at least two cleavages that release the intracellular domain from the cytomembrane and allow it to translocate into the nucleus where it activates its target genes [1]. (scienceexhibitions.org)
Both the receptor and the ligand are membrane-bound but usually expressed on neighbouring cells. (oncotarget.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)

Plexins are widely expressed transmembrane proteins that mediate the effects of semaphorins. (rupress.org)
Their effects are mediated by plexins, a group of transmembrane proteins. (rupress.org)
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)

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)

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)
ERBB is abbreviated from erythroblastic oncogene B, a gene isolated from avian genome. (iiab.me)

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)

The model enables us to quantitatively link HER expression levels to receptor dimerization and activation. (researchhunt.com)

This receptor also binds with TGF-α and VGF (vaccinia virus growth factor). (fgf-4.com)

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)
The primary antihuman antibody against c-erbB-2 oncoprotein (DAKO Diagnostics) was used for IHC. (ijmpo.org)

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)

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)
1 ] [ 2 ] These tumors develop more in middle and late adulthood. (ijmpo.org)
3 ] Most meningiomas are benign tumors, but up to 15% are atypical, and 2% malignant according to the World Health Organization histological criteria reported in 2016. (ijmpo.org)
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)

1, 2 Most studies of MUC1 expression in breast carcinomas have shown that increased membrane MUC1 mucin expression on the apical cell surface is associated with a better prognosis (reviewed in Rahn and colleagues 2 ), whereas circumferential staining in tumour cell cytoplasm is associated with a worse prognosis. (bmj.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)

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)

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)

TPO signals through the c-mpl receptor, and acts as an important regulator of circulating platelets. (fgf-4.com)

Figure 4: Lrig1 controls endogenous signalling through the ErbB pathway. (nature.com)

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)

namely, MUC3, MUC4, MUC12, MUC13, and the recently described mucin MUC17, which share a C-terminal structural domain that consists of two or three epithelial growth factor (EGF)-like regions, a transmembrane segment, and a short cytoplasmic tail. (bmj.com)

EGF signals through a receptor known as c-erbB, which is a class I tyrosine kinase receptor. (fgf-4.com)

Because of this, ErbB-2 is one of the major drug targets for breast cancer and other cancer treatments. (activemotif.com)
[ 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)

While human LIF is active on mouse cells and is widely used in the maintenance of murine ESC to prevent spontaneous differentiation, mouse LIF is not active on human cells due to its inability to bind to the human LIF receptor. (fgf-4.com)

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)

All four ErbB receptor family members are nearly same in the structure having single-chain of modular glycoproteins. (wikipedia.org)
It is a complex process due to the domain specificity and nature of the members of ErbB family. (wikipedia.org)
Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. (rupress.org)
ErbB family members serve as receptors for the epidermal growth factor (EGF) family of growth factors. (rndsystems.com)

AXL, a tyrosine kinase receptor, is commonly overexpressed in several solid tumours and numerous hematopoietic malignancies including acute myeloid leukaemia, acute lymphocytic leukaemia, chronic myeloid leukaemia, chronic lymphocytic leukaemia and multiple myeloma. (cancerindex.org)

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)

A transmembrane mucin that is found in a broad variety of epithelial tissue. (uams.edu)

Figure 5: Lrig1 controls ErbB activation in vivo . (nature.com)

While the importance 23277-43-2 IC50 of HER expression levels has been established for clinical prognosis and drug resistance, the mechanistic link between receptor expression, HER activation and downstream consequences is not as clear yet. (researchhunt.com)

Anatomy8

Organisms1

Diseases1

Chemicals and Drugs39

Analytical, Diagnostic and Therapeutic Techniques and Equipment8

Phenomena and Processes21

Information Science3

Epidermal growth f16

Kinases13

HER211

Phosphorylation8

Ligands10

HER11

Cytoplasmic domain3

Residues2

Extracellular domain2

Tumor3

Protein7

EGFR5

ErbB21

Ligand4

Overexpression2

Proteins3

Kinase inhibitors1

Erythroblastic2

Oncogene1

Dimerization1

Binds1

Antibody2

Inhibitors1

Tumors5

Tumour2

Carcinomas1

RTKs1

Regulator1

Pathway1

Signal transduction1

Consists1

Signals1

Targets2

Human1

Promotes1

Members4

Tumours1

Commonly1

Epithelial1

Vivo1

Prognosis1