Ligand-gated split-kinases

Karla Camacho-Soto, Javier Castillo-Montoya, Blake Tye, Indraneel Ghosh

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The activity of protein kinases are naturally gated by a variety of physiochemical inputs, such as phosphorylation, metal ions, and small molecules. In order to design protein kinases that can be gated by user-defined inputs, we describe a sequence dissimilarity based approach for identifying sites in protein kinases that accommodate 25-residue loop insertion while retaining catalytic activity. We further demonstrate that the successful loop insertion mutants provide guidance for the dissection of protein kinases into two fragments that cannot spontaneously assemble and are thus inactive but can be converted into ligand-gated catalytically active split-protein kinases. We successfully demonstrate the feasibility of this approach with Lyn, Fak, Src, and PKA, which suggests potential generality.

Original languageEnglish (US)
Pages (from-to)3995-4002
Number of pages8
JournalJournal of the American Chemical Society
Issue number10
StatePublished - Mar 12 2014

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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