Biochemical and Structural Insights into Doublecortin-like Kinase Domain 1
Onisha Patel, Weiwen Dai, Mareike Mentzel, Michael DW Griffin, Juliette Serindoux, Yoann Gay, Stefanie Fischer, Shoukat Sterle, Ashleigh Kropp, Christopher J Burns, Matthias Ernst, Michael Buchert, Isabelle S Lucet
STRUCTURE | CELL PRESS | Published : 2016
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..View full abstract
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Awarded by ARC Future Fellowships
Awarded by NHMRC
O.P. and M.G. were supported by ARC Future Fellowships (FT120100056 and FT140100544, respectively). Additional support was received from the Australian Cancer Research Foundation (to I.S.L., W.D., and O.P.). I.S.L. acknowledges support from the Walter and Eliza Hall Institute. This work was also supported by funds from the Operational Infrastructure Support Program provided by the Victorian Government, Australia, and in part by a Project Grant (APP1007523) and a Program Grant (APP487922) from the NHMRC (to M.E. and M.B.). Crystallization experiments were performed at the Bio21 C3 Collaborative Crystallization Centre. We thank beamline staff at the Australian Synchrotron where diffraction data were collected. Mass spectrometry data were collected at the Monash Biomedical Proteomics Facility.