期刊
CELL CHEMICAL BIOLOGY
卷 27, 期 10, 页码 1229-+出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2020.07.011
关键词
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资金
- Hale Family Center for Pancreatic Cancer Research
- Cancer Prevention and Research Institute of Texas [RP170373]
- Welch Foundation [I1829]
- AACR-Bayer Innovation [17-80-44-GRAY]
- DF/HCC GI SPORE Developmental Research Project Award [P50CA127003]
- NIH [U54-HL127365, U24-DK116204, 5U01CA207160]
- American Cancer Society Award [132205-RSG-18-039-01-DMC]
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.
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