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Function
ErbB2(also known as HER2 in human or Neu as an oncogene) is a tyrosine kinase belonging to epidermal growth factor receptor family. It is an orphan receptor, its function in the cell lies in heterodimerization with other members of its family – EGFR, ErbB3 and ErbB4 as a coreceptor. There it acts in transduction of signal by participating in transphosphorylation of kinases intracellular domain. It was found to be preferred interaction partner to other kinases from epidermal growth factor receptor family [3]. It also amplifies the signal and increases affinity for the ligands of its interaction partners [4]. From all its family members, it has the strongest catalytic activity. Effects of this kinase are mostly associated with promotion of proliferation, survival, and cell motility [5].
Disease
Because of its properties, ErbB2 can play a role in cancer development. Its aberrant activity has been associated with breast cancers, in about 20 % of patients [6]. The cause is in majority ErbB2 gene amplification, its expression is in some cases increased up to 100-fold [7]. Though amplification is the major cause of ErbB2 mediated cancer, there have been found numerous mutations that contribute to cancer development, particularly promoting dimerization of kinase [8]. Recent large-scale sequencing efforts have identified oncogenic mutations in the ECD and KD (Greulich et al., 2012; Zabransky et al., 2015; Ross et al., 2016). Mutations in the TMD and JMD have also been reported, albeit at a low frequency (Bose et al., 2013; Yamamoto et al., 2014; Kavuri et al., 2015; Ou et al., 2017; Chang et al., 2018). Somatic mutations can follow after ErbB2 gene amplification, though they arise only in about 3 % of cases of breast cancer [9] . They are also found in other types of cancer, most frequently in bladder, cervical and ampullary cancer [10].
Relevance
Structural highlights
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