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Synthetic Protein Switches pp 307–319Cite as

Engineering Small Molecule Responsive Split Protein Kinases

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1596))

Abstract

The over 500 human protein kinases are estimated to phosphorylate at least one-third of the proteome. This posttranslational modification is of paramount importance to intracellular signaling and its deregulation is linked to numerous diseases. Deciphering the specific cellular role of a protein kinase of interest remains challenging given their structural similarity and potentially overlapping activity. In order to exert control over the activity of user-defined kinases and allow for understanding and engineering of complex signal transduction pathways, we have designed ligand inducible split protein kinases. In this approach, protein kinases are dissected into two fragments that cannot spontaneously assemble and are thus inactive. The two kinase fragments are attached to chemical inducers of dimerization (CIDs) that allow for ligand induced heterodimerization and concomitant activation of kinase activity.

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Acknowledgment

We thank members of the Ghosh lab, Dr. Reena Zutshi, and Luceome Biotechnologies for helpful comments and reagents. Indraneel Ghosh is the CSO at Luceome Biotechnologies, Tucson, AZ. We thank the NIH (1R01GM115595-01) and NSF (CHE-1506091) for supporting this research.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, AZ, 85721, USA

    Javier Castillo-Montoya & Indraneel Ghosh

Authors
  1. Javier Castillo-Montoya
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  2. Indraneel Ghosh
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Corresponding author

Correspondence to Indraneel Ghosh .

Editor information

Editors and Affiliations

  1. Fachbereich Biologie, Technische Universität Darmstadt, Darmstadt, Germany

    Viktor Stein

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Castillo-Montoya, J., Ghosh, I. (2017). Engineering Small Molecule Responsive Split Protein Kinases. In: Stein, V. (eds) Synthetic Protein Switches. Methods in Molecular Biology, vol 1596. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6940-1_19

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  • DOI: https://doi.org/10.1007/978-1-4939-6940-1_19

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6938-8

  • Online ISBN: 978-1-4939-6940-1

  • eBook Packages: Springer Protocols

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