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HER4Human Epidermal Growth Factor Receptor 4
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Varlitinib (ASLAN001) is a highly potent, oral, reversible, small molecule pan-HER inhibitor that targets the human epidermal growth factor receptors HER1, HER2 and HER4. These receptors can be mutated or overexpressed in many tumours, which can cause excessive proliferative activity and uncontrolled growth.
HER3, but not HER4, plays an essential role in the cinicopathology and prognosis of gastric cancer: a meta-analysis.
Immunolocalization of the EGFR, HER2, HER3, HER4 and p53 proteins by immunohistochemistry (IHC) was performed to investigate synchronous expression of these biomarkers.
The HER family of tyrosine kinase receptors consists of EGFR, HER2 (ErbB2), HER3, and HER4. They are responsible for cell survival and proliferation via signalling through the RAS-RAF-ERK and PI3K-PTEN-AKT pathways [224].
Neratinib (HKI-272, Puma Biotechnology Inc., Los Angeles, CA, USA) is an oral pan-HER inhibitor that bonds covalently with a conserved cysteine residue (Cys-773) in the kinase domain of HER, leading to its irreversible inhibition and thus blocking the pathways that lie downstream of EGFR, HER2, and HER4 (Figure 1).
The human epithelial growth factor receptors are a family of four structurally similar homologous members (HER1 to HER4), containing an extracellular binder component, a transmembrane hydrophobic segment, and domain with tyrosine-kinase intracellular activity [20].
Generally, in response to oxidative stress, cardiac endothelial cells release neuregulin, a peptide that activates cardiomyocyte receptors HER4, which in turn dimerizes with HER2 receptors and activates survival pathways (inhibition of apoptosis and reduction of mitochondrial ROS generation through activation of protein kinase B) [63] (Figure 3(a)).
Klagsbrun, "Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation," EMBO Journal, vol.
ErbB proteins are part of the receptor tyrosine kinases family and include four members ErbB1 (also known as EGFR, HER1), ErbB2 (Neu, HER2), ErbB3 (HER3), and ErbB4 (HER4).
However, the binding of ligands to HER1, HER3, or HER4 leads to a preferential dimerization and activation of HER2 (Rubin and Yarden 2001).
EGFR is a member of the erb B family of receptor tyrosine kinases, which is expressed on the cell surface and activated by binding to the ligands including HER1 (EGF/ erb B1), HER1 ( ner / erb B2), HER3 ( erb B3), and HER4 ( erb B4).
The binding affinity of SPINK1 to EGFR was half that of EGF binding affinity, and SPINK1 did not bind to the other members of the family, i.e., HER2, HER3, and HER4 (27).