RRC ID 51996
Author Ohtsuka T, Sakaguchi M, Yamamoto H, Tomida S, Takata K, Shien K, Hashida S, Miyata-Takata T, Watanabe M, Suzawa K, Soh J, Youyi C, Sato H, Namba K, Torigoe H, Tsukuda K, Yoshino T, Miyoshi S, Toyooka S.
Title Interaction of cytokeratin 19 head domain and HER2 in the cytoplasm leads to activation of HER2-Erk pathway.
Journal Sci Rep
Abstract HER2 is a receptor tyrosine kinase and its upregulation via activating mutations or amplification has been identified in some malignant tumors, including lung cancers. Because HER2 can be a therapeutic target in HER2-driven malignancies, it is important to understand the molecular mechanisms of HER2 activation. In the current study, we identified that cytokeratin 19 (KRT19) binds to HER2 at the inside face of plasma membrane. HER2 and KRT19, which were concurrently introduced to a human embryonic kidney 293 T cells, revealed an association with each other and resulted in phosphorylation of HER2 with the subsequent activation of a downstream Erk-associated pathway. A binding assay revealed that both the NH2-terminal head domain of KRT19 and the COOH-terminal domain of HER2 were essential for their binding. To investigate the impact of the interaction between HER2 and KRT19 in lung cancer, we examined their expressions and localizations in lung cancers. We found that KRT19 was highly expressed in HER2-positive lung cancer cells, and KRT19 and HER2 were co-localized at the cell membrane. In conclusion, we found that KRT19 intracellularly binds to HER2, playing a critical role in HER2 activation.
Volume 6
Pages 39557
Published 2016-12-23
DOI 10.1038/srep39557
PII srep39557
PMID 28008968
PMC PMC5180104
MeSH A549 Cells Cell Membrane / metabolism Enzyme Activation ErbB Receptors / metabolism Extracellular Signal-Regulated MAP Kinases / metabolism* Gene Expression Regulation, Enzymologic* Gene Expression Regulation, Neoplastic* HEK293 Cells Humans Keratin-19 / genetics* Keratin-19 / metabolism* Ligands Lung Neoplasms / metabolism MAP Kinase Signaling System Phosphorylation Protein Binding Protein Domains RNA Interference RNA, Small Interfering / metabolism Receptor, ErbB-2 / metabolism*
IF 3.998
Times Cited 11
Human and Animal Cells 293T(RCB2202)