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RTKs in Invertebrates: Lessons in Signal Transduction

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

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Abstract

Receptor tyrosine kinases were first isolated from the Drosophila genome in 1985 (Livneh et al. Cell 40(3):599–607, 1985; Wadsworth et al. Nature 314(6007):178–80, 1985), shortly after the isolation of the vertebrate receptors. Following the initial structural studies of these receptors, additional components in their signaling pathways were identified. Genetic epistasis studies have aided further in determining the linear order of signaling components within the pathway. Importantly, in genetically tractable organisms like Drosophila and C. elegans, the different roles of each receptor during development were deciphered.

This chapter focuses on the insights obtained by studying RTKs in invertebrate organisms. One important observation is that RTK pathways guiding developmental decisions appear to be linear, rather than branched. A second observation is that there is no temporal overlap between distinct RTK pathways within the same cells. Since the activation of MAPK represents a common node to all RTK cascades, it was possible to examine this notion directly. Antibodies that specifically recognize the active, double phosphorylated form of MAPK allow to trace immunohistochemically the dynamic pattern of activation by all RTKs (Gabay et al. Development 124(18):3535–41, 1997). Each aspect of this pattern could be completely removed in a genetic background that specifically eliminates signaling by only one RTK pathway. This implies that the activation of MAPK per se does not provide information on the identity of the activated receptor, and it is the time and tissue context of MAPK activation that defines the target genes that will be induced. The time and place of the activation of each RTK pathway are tightly regulated by the expression of the respective ligands or ligand-processing components. The range of activation is defined by the level of ligand that is secreted and by negative feedback circuits that restrict the range of pathway stimulation.

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Acknowledgments

I am grateful to my lab members that have contributed throughout the years to deciphering many of the paradigms discussed here and to my colleagues for discussions. This work was funded by an ISF converging technologies grant. B.S. is an incumbent of the Hilda and Cecil Lewis chair in Molecular Genetics.

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  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel

    Ben-Zion Shilo

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Correspondence to Ben-Zion Shilo .

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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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Shilo, BZ. (2015). RTKs in Invertebrates: Lessons in Signal Transduction. 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_3

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