Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants

Journal of Neurochemistry

Volumn 103, Issue 1, 2007, Pages 238-247

  Li, Xianting ^a   Tan, Yin Cai ^b   Poulose, Shibu ^a   Olanow, C Warren ^a   Huang, Xin Yun ^b   Yue, Zhenyu ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

Bacterial artificial chromosome transgenics; GTPase; Kinase; Leucine rich repeat kinase 2; Parkinson's disease

Indexed keywords

GUANOSINE TRIPHOSPHATASE; LEUCINE RICH REPEAT KINASE 2; MAPKKK LIKE KINASE; PHOSPHOTRANSFERASE; UNCLASSIFIED DRUG;

ARTICLE; BRAIN TISSUE; CELL CULTURE; COMPARATIVE STUDY; CONTROLLED STUDY; ENZYME ACTIVITY; FAMILIAL DISEASE; FEMALE; GENE MUTATION; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUMAN TISSUE; HYDROLYSIS KINETICS; MOUSE; MUTANT; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN PURIFICATION; TRANSGENIC MOUSE;

AMINO ACID SUBSTITUTION; ANIMALS; CELL LINE; ENZYME ACTIVATION; GTP PHOSPHOHYDROLASES; GUANOSINE TRIPHOSPHATE; HUMANS; MICE; MICE, TRANSGENIC; MUTATION; ORGAN SPECIFICITY; PARKINSON DISEASE; PROTEIN STRUCTURE, TERTIARY; PROTEIN-SERINE-THREONINE KINASES;

BACTERIA (MICROORGANISMS); MUS MUSCULUS;

EID: 34548621385     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/j.1471-4159.2007.04743.x     Document Type: Article

References (24)

1. Biskup S., Moore D. J., Celsi F. et al. (2006) Localization of LRRK2 to membranous and vesicular structures in mammalian brain. Ann. Neurol. 60, 557 569.
2. Bosgraaf L. Van Haastert P. J. (2003) Roc, a Ras/GTPase domain in complex proteins. Biochim. Biophys. Acta 1643, 5 10.
3. Farnsworth C. L., Marshall M. S., Gibbs J. B., Stacey D. W. Feig L. A. (1991) Preferential inhibition of the oncogenic form of RasH by mutations in the GAP binding/"effector" domain. Cell 64, 625 633.
4. Galter D., Westerlund M., Carmine A., Lindqvist E., Sydow O. Olson L. (2006) LRRK2 expression linked to dopamine-innervated areas. Ann. Neurol. 59, 714 719.
5. Giasson B. I., Covy J. P., Bonini N. M., Hurtig H. I., Farrer M. J., Trojanowski J. Q. Van Deerlin V. M. (2006) Biochemical and pathological characterization of Lrrk2. Ann. Neurol. 59, 315 322.
6. Gloeckner C. J., Kinkl N., Schumacher A., Braun R. J., O'Neill E., Meitinger T., Kolch W., Prokisch H. Ueffing M. (2006) The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum. Mol. Genet. 15, 223 232.
7. Greggio E., Jain S., Kingsbury A. et al. (2006) Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol. Dis. 23, 329 341.
8. Guo D., Tan Y. C., Wang D., Madhusoodanan K. S., Zheng Y., Maack T., Zhang J. J. Huang X. Y. (2007) A Rac-cGMP signaling pathway. Cell 128, 341 355.
9. Hart M. J., Polakis P. G., Evans T. Cerione R. A. (1990) The identification and characterization of an epidermal growth factor-stimulated phosphorylation of a specific low molecular weight GTP-binding protein in a reconstituted phospholipid vesicle system. J. Biol. Chem. 265, 5990 6001.
10. Heintz N. (2001) BAC to the future: the use of bac transgenic mice for neuroscience research. Nat. Rev. Neurosci. 2, 861 870.
11. Ito G., Okai T., Fujino G., Takeda K., Ichijo H., Katada T. Iwatsubo T. (2007) GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. Biochemistry 46, 1380 1388.
12. Macleod D., Dowman J., Hammond R., Leete T., Inoue K. Abeliovich A. (2006) The familial parkinsonism gene LRRK2 regulates neurite process morphology. Neuron 52, 587 593.
13. Mata I. F., Wedemeyer W. J., Farrer M. J., Taylor J. P. Gallo K. A. (2006) LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci. 29, 286 293.
14. McNaught K. S., Olanow C. W., Halliwell B., Isacson O. Jenner P. (2001) Failure of the ubiquitin-proteasome system in Parkinson's disease. Nat. Rev. Neurosci. 2, 589 594.
15. Melrose H., Lincoln S., Tyndall G., Dickson D. Farrer M. (2006) Anatomical localization of leucine-rich repeat kinase 2 in mouse brain. Neuroscience 139, 791 794.
16. Paisan-Ruiz C., Jain S., Evans E. W. et al. (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44, 595 600.
17. Smith W. W., Pei Z., Jiang H., Dawson V. L., Dawson T. M. Ross C. A. (2006) Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat. Neurosci. 9, 1231 1233.
18. Stenmark H. Olkkonen V. M. (2001) The Rab GTPase family. Genome Biol. 2, REVIEWS3007.
19. Taymans J. M., Van den Haute C. Baekelandt V. (2006) Distribution of PINK1 and LRRK2 in rat and mouse brain. J. Neurochem. 98, 951 961.
20. West A. B., Moore D. J., Biskup S., Bugayenko A., Smith W. W., Ross C. A., Dawson V. L. Dawson T. M. (2005) Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc. Natl Acad. Sci. USA 102, 16842 16847.
21. Xia C., Ma W., Stafford L. J., Liu C., Gong L., Martin J. F. Liu M. (2003) GGAPs, a new family of bifunctional GTP-binding and GTPase-activating proteins. Mol. Cell Biol. 23, 2476 2488.
22. Yang X. W., Model P. Heintz N. (1997) Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome. Nat. Biotechnol. 15, 859 865.
23. Zhang B., Chernoff J. Zheng Y. (1998) Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA. J. Biol. Chem. 273, 8776 8782.
24. Zimprich A., Biskup S., Leitner P. et al. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44, 601 607.