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Mutation-introduced dimerization of receptor tyrosine kinases: from protein structure aberrations to carcinogenesis

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Tumor Biology

Abstract

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.

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Acknowledgments

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).

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    Authors and Affiliations

    1. Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, No. 6 Tiantan Xili, Dongcheng, Beijing, 100050, People’s Republic of China

      Huimin Hu, Yanwei Liu & Tao Jiang

    2. Chinese Glioma Cooperative Group (CGCG), 6 Tiantanxi Li, Beijing, 100050, China

      Huimin Hu, Yanwei Liu & Tao Jiang

    3. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng, Beijing, 100050, People’s Republic of China

      Tao Jiang

    4. Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, China

      Tao Jiang

    Authors
    1. Huimin Hu
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    2. Yanwei Liu
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    3. Tao Jiang
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    Correspondence to Tao Jiang.

    Additional information

    Huimin Hu and Yanwei Liu contributed equally to this work.

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    Hu, H., Liu, Y. & Jiang, T. Mutation-introduced dimerization of receptor tyrosine kinases: from protein structure aberrations to carcinogenesis. Tumor Biol. 36, 1423–1428 (2015). https://doi.org/10.1007/s13277-015-3287-4

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    • DOI: https://doi.org/10.1007/s13277-015-3287-4

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