科研之友
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摘要
Background: The EGF receptor, ErbB2, and ErbB3 can interact to form dimers. Results: Analyses of these interactions show that ErbB3 interacts strongly with ErbB2 but weakly with the EGF receptor. All ErbB receptor interactions are enhanced by erlotinib and lapatinib. Conclusion: ErbB3 binds and is functionally affected by tyrosine kinase inhibitors. Significance: Tyrosine kinase inhibitors restructure the network of ErbB interactions. %26lt;br%26gt;ErbB3 is a member of the ErbB family of receptor tyrosine kinases. It is unique because it is the only member of the family whose kinase domain is defective. As a result, it is obliged to form heterodimers with other ErbB receptors to signal. In this study, we characterized the interaction of ErbB3 with the EGF receptor and ErbB2 and assessed the effects of Food and Drug Administration-approved therapeutic agents on these interactions. Our findings support the concept that ErbB3 exists in preformed clusters that can be dissociated by NRG-1 and that it interacts with other ErbB receptors in a distinctly hierarchical fashion. Our study also shows that all pairings of the EGF receptor, ErbB2, and ErbB3 form ligand-independent dimers/oligomers. The small-molecule tyrosine kinase inhibitors erlotinib and lapatinib differentially enhance the dimerization of the various ErbB receptor pairings, with the EGFR/ErbB3 heterodimer being particularly sensitive to the effects of erlotinib. The data suggest that the physiological effects of these drugs may involve not only inhibition of tyrosine kinase activity but also a dynamic restructuring of the entire network of receptors.
- 出版日期2013-10-18
