Strategies for Engineering and Rewiring Kinase Regulation

James W. McCormick, David Pincus, Orna Resnekov, Kimberly A. Reynolds

Research output: Contribution to journalReview article

Abstract

Eukaryotic protein kinases (EPKs) catalyze the transfer of a phosphate group onto another protein in response to appropriate regulatory cues. In doing so, they provide a primary means for cellular information transfer. Consequently, EPKs play crucial roles in cell differentiation and cell-cycle progression, and kinase dysregulation is associated with numerous disease phenotypes including cancer. Nonnative cues for synthetically regulating kinases are thus much sought after, both for dissecting cell signaling pathways and for pharmaceutical development. In recent years advances in protein engineering and sequence analysis have led to new approaches for manipulating kinase activity, localization, and in some instances specificity. These tools have revealed fundamental principles of intracellular signaling and suggest paths forward for the design of therapeutic allosteric kinase regulators.

Original languageEnglish (US)
Pages (from-to)259-271
Number of pages13
JournalTrends in biochemical sciences
Volume45
Issue number3
DOIs
StatePublished - Mar 2020

Keywords

  • allostery
  • coevolution
  • kinase
  • optogenetics
  • phosphoregulation
  • sector

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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