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Evolution of Receptor Tyrosine Kinases

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

Abstract

Receptor tyrosine kinases (RTKs) hold a key position in the complex network of intercellular communication of multicellular organisms. The origins of the 58 RTKs in the human genome can therefore be traced back to the basis of metazoans. This chapter provides a reconstruction of the evolutionary history of the mammalian RTK repertoire and the interrelationships of RTK families and their individual members. Early on in metazoan evolution, a basic set of nine RTKs was already present, represented in extant invertebrates by one member of the EGF receptor, insulin receptor, FGF receptor, and EPH receptor families, one RTK of the PDGF/VEGF receptor superfamily, DDR and ROR families, and a MuSK- and PTK7-type receptor. This set of basic receptors was then expanded to 16 RTKs in the ancestor of the chordates. The full complement of the human RTK families is the result of two whole genome duplications that occurred in early vertebrate evolution. With a third whole genome duplication, fish have even more RTKs. The gain in RTK genes in the course of evolution mirrors the increasing complexity of cell types, cell functions, and intracrine, autocrine, juxtacrine, paracrine, and endocrine cellular interactions.

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Acknowledgments

We gratefully acknowledge the support by the Deutsche Forschungsgemeinschaft (DFG) to MS and Agence Nationale de la Recherche (ANR) to JNV. Due to restrictions in space and in light of the plethora of publications on RTKs, only a selection of references could be considered. We apologize to all whose work has not been cited or discussed and declare that such omissions do not reflect any validation of the relevance and quality of the research reported there.

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Authors and Affiliations

  1. Department of Physiological Chemistry, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany

    Manfred Schartl Ph.D.

  2. Institut de Génomique Fonctionnelle, UMR5242 CNRS/INRA/University of Lyon I/Ecole Normale Supérieure, 46 allée d’Italie, Lyon, France

    Jean-Nicolas Volff & Frederic Brunet

Authors
  1. Manfred Schartl Ph.D.
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  2. Jean-Nicolas Volff
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  3. Frederic Brunet
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Corresponding author

Correspondence to Manfred Schartl Ph.D. .

Editor information

Editors and Affiliations

  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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Schartl, M., Volff, JN., Brunet, F. (2015). Evolution 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_2

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