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

doi:10.1016/j.chembiol.2020.07.011

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 journal › Article › peer-review

16 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 language	English (US)
Pages (from-to)	1229-1240.e4
Journal	Cell Chemical Biology
Volume	27
Issue number	10
DOIs	https://doi.org/10.1016/j.chembiol.2020.07.011
State	Published - 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

Access to Document

10.1016/j.chembiol.2020.07.011

Cite this

@article{0c4d3a2884b34e63aae7dd6297589fc5,

title = "Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing",

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.",

keywords = "cancer, doublecortin-like kinase 1, kinase inhibitor, mass spectrometry, phosphoproteomics, signal transduction, structural biology",

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

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",

year = "2020",

month = oct,

day = "15",

doi = "10.1016/j.chembiol.2020.07.011",

language = "English (US)",

volume = "27",

pages = "1229--1240.e4",

journal = "Cell Chemical Biology",

issn = "2451-9456",

publisher = "Elsevier Inc.",

number = "10",

}

TY - JOUR

T1 - Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing

AU - Liu, Yan

AU - Ferguson, Fleur M.

AU - Li, Lianbo

AU - Kuljanin, Miljan

AU - Mills, Caitlin E.

AU - Subramanian, Kartik

AU - Harshbarger, Wayne

AU - Gondi, Sudershan

AU - Wang, Jinhua

AU - Sorger, Peter K.

AU - Mancias, Joseph D.

AU - Gray, Nathanael S.

AU - Westover, Kenneth D.

PY - 2020/10/15

Y1 - 2020/10/15

N2 - 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.

AB - 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.

KW - cancer

KW - doublecortin-like kinase 1

KW - kinase inhibitor

KW - mass spectrometry

KW - phosphoproteomics

KW - signal transduction

KW - structural biology

UR - http://www.scopus.com/inward/record.url?scp=85089963741&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85089963741&partnerID=8YFLogxK

U2 - 10.1016/j.chembiol.2020.07.011

DO - 10.1016/j.chembiol.2020.07.011

M3 - Article

C2 - 32755567

AN - SCOPUS:85089963741

SN - 2451-9456

VL - 27

SP - 1229-1240.e4

JO - Cell Chemical Biology

JF - Cell Chemical Biology

IS - 10

ER -

Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this