Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing

Yan Liu, Fleur M. Ferguson, Lianbo Li, Miljan Kuljanin, Caitlin E. Mills, Kartik Subramanian, Wayne Harshbarger, Sudershan Gondi, Jinhua Wang, Peter K. Sorger, Joseph D. Mancias, Nathanael S. Gray, Kenneth D. Westover

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Doublecortin-like kinase 1 (DCLK1) is critical for neurogenesis, but overexpression is also observed in multiple cancers and is associated with poor prognosis. Nevertheless, the function of DCLK1 in cancer, especially the context-dependent functions, are poorly understood. We present a “toolkit” that includes the DCLK1 inhibitor DCLK1-IN-1, a complementary DCLK1-IN-1-resistant mutation G532A, and kinase dead mutants D511N and D533N, which can be used to investigate signaling pathways regulated by DCLK1. Using a cancer cell line engineered to be DCLK1 dependent for growth and cell migration, we show that this toolkit can be used to discover associations between DCLK1 kinase activity and biological processes. In particular, we show an association between DCLK1 and RNA processing, including the identification of CDK11 as a potential substrate of DCLK1 using phosphoproteomics.

Original languageEnglish (US)
Pages (from-to)1229-1240.e4
JournalCell Chemical Biology
Volume27
Issue number10
DOIs
StatePublished - Oct 15 2020

Keywords

  • cancer
  • doublecortin-like kinase 1
  • kinase inhibitor
  • mass spectrometry
  • phosphoproteomics
  • signal transduction
  • structural biology

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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