Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/17631
Title: Biochemical and Structural Insights into Doublecortin-like Kinase Domain 1.
Austin Authors: Patel, Onisha;Dai, Weiwen;Mentzel, Mareike;Griffin, Michael D W;Serindoux, Juliette;Gay, Yoann;Fischer, Stefanie;Sterle, Shoukat;Kropp, Ashleigh;Burns, Christopher J;Ernst, Matthias ;Buchert, Michael;Lucet, Isabelle S
Affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia
Issue Date: 6-Sep-2016
metadata.dc.date: 2016-08-18
Publication information: Structure (London, England : 1993) 2016; 24(9): 1550-1561
Abstract: 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/17631
DOI: 10.1016/j.str.2016.07.008
ORCID: 0000-0002-6399-1177
PubMed URL: 27545623
Type: Journal Article
Appears in Collections:Journal articles

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