Biochemical and Structural Insights into Doublecortin-like Kinase Domain 1

Onisha Patel, Weiwen Dai, Mareike Mentzel, Michael D W Griffin, Juliette Serindoux, Yoann Gay, Stefanie Fischer, Shoukat Afshar-Sterle, Ashleigh Kropp, Christopher J Burns, Matthias Ernst, Michael Buchert, Isabelle S. Lucet

Research output: Contribution to journalArticleResearchpeer-review

50 Citations (Scopus)


Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that belongs to the family of microtubule-associated proteins. Originally identified for its role in neurogenesis, DCLK1 has recently been shown to regulate biological processes outside of the CNS. DCLK1 is among the 15 most common putative driver genes for gastric cancers and is highly mutated across various other human cancers. However, our present understanding of how DCLK1 dysfunction leads to tumorigenesis is limited. Here, we provide evidence that DCLK1 kinase activity negatively regulates microtubule polymerization. We present the crystal structure of the DCLK1 kinase domain at 1.7 Å resolution, providing detailed insight into the ATP-binding site that will serve as a framework for future drug design. This structure also allowed for the mapping of cancer-causing mutations within the kinase domain, suggesting that a loss of kinase function may contribute to tumorigenesis.

Original languageEnglish
Pages (from-to)1550-1561
Number of pages12
Issue number9
Publication statusPublished - 6 Sept 2016
Externally publishedYes

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