Mutation-introduced dimerization of receptor tyrosine kinases: from protein structure aberrations to carcinogenesis
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Cancer is the greatest challenge to human health in our era. Perturbations of receptor tyrosine kinase (RTK) function contribute to a large chunk of cancer etiology. Current evidence supports that mutations in RTKs mediate receptor dimerization and result in ligand-independent kinase activity and tumorigenesis, indicating that mutation-introduced receptor dimerization is a critical component of oncogenesis RTK mutations. However, there are no specialized reviews of this important principle. In the current review, we discuss the physiological and harmless RTK function and subsequently examine mutation-introduced dimerization of RTKs and the role of these mutations in tumorigenesis. We also summarize the protein structure characteristics that are important for dimerization and introduce research methods and tools to predict and validate the existence of oncogenic mutations introduced by dimerization in RTKs.
KeywordsReceptor tyrosine kinases Mutation Dimerization Oncogenicity Gene rearrangement Protein structure alteration Oncogenesis
This study was supported by grants from the National High Technology Research and Development Program (No. 2012AA02A508), the National 973 program (No. 2011CB707804), and the National Nature Science Foundation of China (No. 81201993 and No. 81272804).
Conflicts of interest
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