Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2 (original) (raw)
This is a preview of subscription content, access via your institution
References
- Gandhi, P.N., Chen, S.G. & Wilson-Delfosse, A.L. J. Neurosci. Res. 87, 1283–1295 (2009).
Article CAS PubMed PubMed Central Google Scholar - Zimprich, A. et al. Neuron 44, 601–607 (2004).
Article CAS PubMed Google Scholar - Paisán-Ruíz, C. et al. Neuron 44, 595–600 (2004).
Article PubMed Google Scholar - Healy, D.G. et al. Lancet Neurol. 7, 583–590 (2008).
Article CAS PubMed PubMed Central Google Scholar - Dächsel, J.C. & Farrer, M.J. Arch. Neurol. 67, 542–547 (2010).
Article PubMed Google Scholar - Greggio, E. & Cookson, M.R. ASN Neuro 1, e00002 (2009).
Article PubMed PubMed Central Google Scholar - Covy, J.P. & Giasson, B.I. Biochem. Biophys. Res. Commun. 378, 473–477 (2009).
Article CAS PubMed Google Scholar - Anand, V.S. et al. FEBS J. 276, 466–478 (2009).
Article CAS PubMed Google Scholar - Nichols, R.J. et al. Biochem. J. 424, 47–60 (2009).
Article CAS PubMed Google Scholar - Lee, B.D. et al. Nat. Med. 16, 998–1000 (2010).
Article CAS PubMed PubMed Central Google Scholar - Goldstein, D.M., Gray, N.S. & Zarrinkar, P.P. Nat. Rev. Drug Discov. 7, 391–397 (2008).
Article CAS PubMed Google Scholar - Fabian, M.A. et al. Nat. Biotechnol. 23, 329–336 (2005).
Article CAS PubMed Google Scholar - Karaman, M.W. et al. Nat. Biotechnol. 26, 127–132 (2008).
Article CAS PubMed Google Scholar - Bain, J. et al. Biochem. J. 408, 297–315 (2007).
Article CAS PubMed PubMed Central Google Scholar - Patricelli, M.P. et al. Biochemistry 46, 350–358 (2007).
Article CAS PubMed Google Scholar - Nichols, R.J. et al. Biochem. J. 430, 393–404 (2010).
Article CAS PubMed Google Scholar - Dzamko, N. et al. Biochem. J. 430, 405–413 (2010).
Article CAS PubMed Google Scholar - Alegre-Abarrategui, J. et al. Hum. Mol. Genet. 18, 4022–4034 (2009).
Article CAS PubMed PubMed Central Google Scholar - Greggio, E. et al. Neurobiol. Dis. 23, 329–341 (2006).
Article CAS PubMed Google Scholar - Alessi, D.R. et al. J. Biol. Chem. 270, 27489–27494 (1995).
Article CAS PubMed Google Scholar - Cuenda, A. et al. FEBS Lett. 364, 229–233 (1995).
Article CAS PubMed Google Scholar - Vlahos, C.J. et al. J. Biol. Chem. 269, 5241–5248 (1994).
CAS PubMed Google Scholar
Acknowledgements
We wish to thank staff at the National Centre for Protein Kinase Profiling (http://www.kinase-screen.mrc.ac.uk) for undertaking Dundee kinase specificity screening, F. Hentati (Institut National de Neurologie, Tunisia) and A. Reith (GlaxoSmithKline Pharmaceuticals Research and Development) for providing EBV immortalized human lymphoblastoid cells, P. Bamborough (GlaxoSmithKline Pharmaceuticals Research and Development) for providing LRRK2 homology model and the antibody purification teams (Division of Signal Transduction Therapy (DSTT), University of Dundee) coordinated by H. McLauchlan and J. Hastie for generation of antibodies. This work was supported by US National Institutes of Health grant P41 GM079575-03 (N.S.G.), the Medical Research Council Technology Industry Collaboration Award and a National Health and Medical Research Council postdoctoral fellowship (N.D.), the Medical Research Council (D.R.A.), the Michael J. Fox Foundation for Parkinson's Disease Research (D.R.A.), the pharmaceutical companies supporting the DSTT (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KgaA and Pfizer) (D.R.A.), the US National Institutes of Health grants CA079871 and CA114059 (J.-D.L.) and funds from the Tobacco-Related Disease Research Program of the University of California, 19XT-0084, (J.-D.L.).
Author information
Author notes
- Xianming Deng and Nicolas Dzamko: These authors contributed equally to this work.
Authors and Affiliations
- Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Xianming Deng, Qingsong Liu & Nathanael S Gray - Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA
Xianming Deng, Qingsong Liu & Nathanael S Gray - MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee, Scotland
Nicolas Dzamko, Paul Davies & Dario R Alessi - Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee, Dundee, Scotland
Alan Prescott - Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA
Qingkai Yang & Jiing-Dwan Lee - ActivX Biosciences, La Jolla, California, USA
Matthew P Patricelli & Tyzoon K Nomanbhoy
Authors
- Xianming Deng
You can also search for this author inPubMed Google Scholar - Nicolas Dzamko
You can also search for this author inPubMed Google Scholar - Alan Prescott
You can also search for this author inPubMed Google Scholar - Paul Davies
You can also search for this author inPubMed Google Scholar - Qingsong Liu
You can also search for this author inPubMed Google Scholar - Qingkai Yang
You can also search for this author inPubMed Google Scholar - Jiing-Dwan Lee
You can also search for this author inPubMed Google Scholar - Matthew P Patricelli
You can also search for this author inPubMed Google Scholar - Tyzoon K Nomanbhoy
You can also search for this author inPubMed Google Scholar - Dario R Alessi
You can also search for this author inPubMed Google Scholar - Nathanael S Gray
You can also search for this author inPubMed Google Scholar
Contributions
N.S.G. conceived and directed the chemistry effort. X.D. performed the chemical synthesis and structure-activity relationship analysis. D.R.A. conceived and directed the biology effort. N.D. performed the biology experimental research with assistance from A.P. (confocal microscopy and live cell imaging). P.D. performed the SHSY5Y experiment. Q.L. performed the modeling study. Q.Y. and J.-D.L. performed the MAPK7 cellular assay. M.P.P. and T.K.N. performed the KiNativ selectivity profiling and data analysis. X.D., N.D., D.R.A. and N.S.G. co-wrote the paper. All authors read and edited the manuscript.
Corresponding authors
Correspondence toDario R Alessi or Nathanael S Gray.
Ethics declarations
Competing interests
M.P.P. and T.K.N. are employees of ActivX Biosciences.
Supplementary information
Rights and permissions
About this article
Cite this article
Deng, X., Dzamko, N., Prescott, A. et al. Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2.Nat Chem Biol 7, 203–205 (2011). https://doi.org/10.1038/nchembio.538
- Received: 10 September 2010
- Accepted: 29 January 2011
- Published: 06 March 2011
- Issue Date: April 2011
- DOI: https://doi.org/10.1038/nchembio.538