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Nuclear Functions of Receptor Tyrosine Kinases

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Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease

Abstract

Receptor tyrosine kinases (RTKs) are well-known cell surface receptors that play important roles in normal cellular processes by binding to many growth factors and cytokines. Abnormal expression and mutations of these RTKs have been implicated in the development of many diseases including cancers. More recently, accumulated studies have shown that 11 of total 20 RTK subfamilies are detected in the nucleus, including the EGFR family, VEGFR family, FGFR family, insulin receptor family, Eph family, HGF receptor family, and ROR family as well as Trk, Ryk, and Mer receptor tyrosine kinases. These observations of nuclear-localized RTKs and functional studies demonstrate that RTKs function not only on the cell surface but also in the nucleus. Thus, it has become increasingly important to understand how the cell surface receptors are trafficked to the nucleus and how these receptors function in the nucleus. Several studies have shown that nuclear RTKs are involved in transcriptional regulation, DNA damage response, DNA replication, and drug resistance. In addition, a membrane-associated trafficking mechanism has been reported, which provides a comprehensive pathway for nuclear translocation of EGFR. This trafficking route may serve as a general mechanism for other cell surface receptors for the nuclear transport. In this chapter, we will focus the functional study of nuclear RTKs and summarize the physiological and pathological functions of RTKs in the nucleus.

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Acknowledgments

This study was funded in part by grants from the National Institutes of Health (grants R01 CA109311, PO1 CA099031, and CCSG CA16672), National Breast Cancer Foundation, Inc., Breast Cancer Research Foundation, Patel Memorial Breast Cancer Endowment Fund, The University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund, Ministry of Health and Welfare, China Medical University Hospital Cancer Research Center of Excellence (MOHW103- TD-B-111-03; Taiwan), Program for Stem Cell and Regenerative Medicine Frontier Research (NSC102-2321-B-039-001; Taiwan), International Research-Intensive Centers of Excellence in Taiwan (NSC103-2911-I-002-303), and Center for Biological Pathways.

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Authors and Affiliations

  1. Department of Molecular and Cellular Oncology, Unit 0079, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Yi Du, Jennifer L. Hsu, Ying-Nai Wang & Mien-Chie Hung Ph.D.

  2. Center for Molecular Medicine, China Medical University, Taichung, Taiwan

    Jennifer L. Hsu, Ying-Nai Wang & Mien-Chie Hung Ph.D.

  3. Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan

    Jennifer L. Hsu, Ying-Nai Wang & Mien-Chie Hung Ph.D.

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  1. Yi Du
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  2. Jennifer L. Hsu
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  3. Ying-Nai Wang
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  4. Mien-Chie Hung Ph.D.
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Correspondence to Mien-Chie Hung Ph.D. .

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  1. Department of Human Oncology, University of Wisconsin, Madison, Wisconsin, USA

    Deric L. Wheeler

  2. Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

    Yosef Yarden

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Du, Y., Hsu, J.L., Wang, YN., Hung, MC. (2015). Nuclear Functions of Receptor Tyrosine Kinases. In: Wheeler, D., Yarden, Y. (eds) Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2053-2_5

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