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HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. But contrary to other members of the ERBB family, HER2 does not directly bind ligand. HER2 activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high, for instance in cancer. [8]
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). In many cancer types, mutations affecting EGFR expression or activity could result in cancer. [6]
Activation of the tyrosine kinase domain leads to the activation of the whole range of downstream signaling pathways like PLCγ, ERK 1/2, p38 MAPK, PI3-K/Akt and more with the cell. [ 17 ] [ 18 ] When not bound to a ligand, the extracellular regions of ErbB1, ErbB3, and ErbB4 are found in a tethered conformation in which a 10-amino-acid-long ...
The human ERBB3 gene is located on the long arm of chromosome 12 (12q13). It is encoded by 23,651 base pairs and translates into 1342 amino acids. [5]During human development, ERBB3 is expressed in skin, bone, muscle, nervous system, heart, lungs, and intestinal epithelium. [6]
Trastuzumab downregulates neuregulin-1 (NRG-1), which is essential for the activation of cell survival pathways in cardiomyocytes and the maintenance of cardiac function. NRG-1 activates the MAPK pathway and the PI3K/AKT pathway as well as focal adhesion kinases (FAK). These are all significant for the function and structure of cardiomyocytes.
The bundle of His (BH) [1]: 58 or His bundle (HB) [1]: 232 (/ h ɪ s / "hiss" [2]) is a collection of heart muscle cells specialized for electrical conduction.As part of the electrical conduction system of the heart, it transmits the electrical impulses from the atrioventricular node (located between the atria and the ventricles) to the point of the apex of the fascicular branches via the ...
These adaptor proteins link RTK activation to downstream signal transduction pathways, such as the MAP kinase signalling cascade. [2] An example of a vital signal transduction pathway involves the tyrosine kinase receptor, c-met, which is required for the survival and proliferation of migrating myoblasts during myogenesis. A lack of c-met ...
PARs are activated by the action of serine proteases such as thrombin (acts on PARs 1, 3 and 4) and trypsin (PAR 2). [6] These enzymes cleave the N-terminus of the receptor, which in turn acts as a tethered ligand. In the cleaved state, part of the receptor itself acts as the agonist, causing a physiological response.