Engineering small molecule responsive split protein kinases

Javier Castillo-Montoya, Indraneel Ghosh

Research output: Chapter in Book/Report/Conference proceedingChapter

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.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages307-319
Number of pages13
Volume1596
DOIs
StatePublished - 2017

Publication series

NameMethods in Molecular Biology
Volume1596
ISSN (Print)10643745

Fingerprint

Protein Kinases
Phosphotransferases
Ligands
Dimerization
Proteome
Post Translational Protein Processing
Signal Transduction

Keywords

  • Chemical inducer of dimerization
  • Ligand gating
  • Protein kinase
  • Split kinase
  • Split protein

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Castillo-Montoya, J., & Ghosh, I. (2017). Engineering small molecule responsive split protein kinases. In Methods in Molecular Biology (Vol. 1596, pp. 307-319). (Methods in Molecular Biology; Vol. 1596). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-6940-1_19

Engineering small molecule responsive split protein kinases. / Castillo-Montoya, Javier; Ghosh, Indraneel.

Methods in Molecular Biology. Vol. 1596 Humana Press Inc., 2017. p. 307-319 (Methods in Molecular Biology; Vol. 1596).

Research output: Chapter in Book/Report/Conference proceedingChapter

Castillo-Montoya, J & Ghosh, I 2017, Engineering small molecule responsive split protein kinases. in Methods in Molecular Biology. vol. 1596, Methods in Molecular Biology, vol. 1596, Humana Press Inc., pp. 307-319. https://doi.org/10.1007/978-1-4939-6940-1_19
Castillo-Montoya J, Ghosh I. Engineering small molecule responsive split protein kinases. In Methods in Molecular Biology. Vol. 1596. Humana Press Inc. 2017. p. 307-319. (Methods in Molecular Biology). https://doi.org/10.1007/978-1-4939-6940-1_19
Castillo-Montoya, Javier ; Ghosh, Indraneel. / Engineering small molecule responsive split protein kinases. Methods in Molecular Biology. Vol. 1596 Humana Press Inc., 2017. pp. 307-319 (Methods in Molecular Biology).
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