Methods

Details Methods Methods

2011-05-24

2011-05-24

Monshipouri, Maryam (Department: 1656)

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving transferase

Reexamination Certificate

active

07947468

ABSTRACT:
A method for identifying a compound expected to be useful in modulating a LRRK2 protein kinase activity, the method comprising the steps of (1) determining whether a test compound modulates the protein kinase activity of a LRRK2 polypeptide on a substrate Ezrin/Radixin/moesin (ERM) family polypeptide and (2) selecting a compound which modulates the LRRK2 polypeptide protein kinase activity. Such a compound may be useful in treating Parkinson's Disease or Parkinsonism. A catalytically active fragment of LRRK2 is identified, requiring the GTPase, COR and kinase domains as well as the WD_40-like motif and C-terminal tail.

REFERENCES:
patent: 2003/0166222 (2003-09-01), Meyers
patent: 2004/0265849 (2004-12-01), Cargill et al.
patent: 2004074485 (2004-09-01), None
patent: 2007104763 (2007-09-01), None
patent: 2008091799 (2008-07-01), None
patent: 2008122789 (2008-10-01), None
Marin, The Parkinson Disease Gene LRRK2: Evolutionary and Structural Insights, Mol. Biol. Evol., 2006, 2423-2433, 23(12), Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Goldberg et al, Identification of four candidate cGMP targets in Dictyostelium, PNAS, 2002, 6749-6754, vol. 99, No. 10, Boston Biomedical Research Institute.
West et al, Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity, PNAS, 2005, 16842-19847, vol. 102, No. 46, Institute for Cell Engineering, Departments of Neurology, Neuroscience, and Physiology.
Bosgraaf et al, A novel cGMP signalling pathway mediating myosin phosphorylation and chemotaxis in Dictyostelium, The EMBO Journal, 2002, 4560-4570, vol. 21, No. 17, Department of Biochemistry, University of Groningen.
Tran Quang et al, Ezrin function is required for ROCK-mediated fibroblast transformation by the Net and Dbl oncogenes, The EMBO Journal, 2000, 4565-4576, vol. 19, No. 17, Imperial Cancer Research Fund Laboratories.
Cohen et al, Kestrel: a powerful method for identifying the physiological substrates of protein kinases, Biochemical Journal, 2006, 1-6, 393, MRC protein Phosphorylation Unit.
Gary et al, Ezrin Self-Association Involves Binding of an N-Terminal Domain to a Normally Masked C-Terminal Domain that Includes the F-Actin Binding Site, Molecular Biology of the Cell, 1995, 1061-1075, vol. 6, The American Society for Cell Biology.
Pestonjamasp et al, Moesin, Ezrin, and p205 Are Actin-binding Proteins Associated with Neurophil Plasma Membranes, Molecular Biology of the Cell, 1995, 247-259, vol. 6, The American Society for Cell Biology.
Nakamura et al, Regulation of F-Actin Binding to Platelet Moesin in Vitro by Both Phosphorylation of Threonine 558 and Polyphosphatidylinositides, Molecular Biology of the Cell, 1999, 2669-2685, vol. 10, The American Society for Cell Biology.
Turunen et al, Ezrin Has a COOH-Terminal Actin-binding Site That is Conserved in the Ezrin Protein Family, The Journal of Cell Biology, 1994, 1445-1453, vol. 126, No. 6, The Rockefeller University Press.
Matsui et al, Rho-Kinase Phosphorylates COOH-terminal Threonines of Ezrin/Radixin/Moesin (ERM) Proteins and Regulates Their Head-to-Tail Association, The Journal of Cell Biology, 1998, 647-657, vol. 140, No. 3, The Rockefeller University Press.
Paglini et al, Suppression of Radixin and Moesin Alters Growth Cone Morphology, Motility, and process Formation in Primary Cultured Neurons, The Journal of Cell Biology, 1998, 443-455, vol. 143, No. 2, The Rockefeller University Press.
Huang et al, Replacement of Threonine 558, a Critical Site of Phosphorylation of Moesin in Vivo, with Aspartate Activates F-actin Binding of Moesin, The Journal of Biological Chemistry, 1999, 12803-12810, vol. 274, No. 18, The American Society for Biochemistry and Molecular Biology, Inc.
Oshiro et al, Phosphorylation of Moesin by Rho-associated Kinase (Rho-kinase) Plays a Crucial Role in the Formation of Microvilli-like Structures, The Journal of Biological Chemistry, 1998, 34663-34666, vol. 273, No. 52, The American Society for Biochemistry and Molecular Biology, Inc.
McClatchey et al, Membraine organization and tumorigenesis—the NF2 tumor suppressor, Merlin, Genes & Development, 2005, 2265-2277, 19, Massachusetts General Hospital, Center for Cancer Research and Harvard Medical School, Department of Pathology, Charlestown.
West et al, Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-bindind and kinase activities to neuronal toxicity, Human Molecular Genetics, 2007, 223-232, vol. 16, No. 2, Oxford University Press.
Gloeckner et al, The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity, Human Molecular Genetics, 2006, 223-232, vol. 15, No. 2, Oxford University Press.
Jaleel et al, LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity, Biochemical Journal, 2007, 307-317, 405, Biochemical Society.
Polesello et al, Small is beautiful: what flies tell us about ERM protein function in development, Trends in Cell Biology, 2004, vol. 14, No. 6, pp. 294-302, Centre de Biologie du Developpement, France.
Taylor et al, LRRK2: a common pathway for parkinsonism, pathogenesis and prevention?, Trends in Molecular Medicine, 2006, vol. 12, No. 2, pp. 76-82, Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville.
Mata et al, LRRK2 in Parkinson's disease: protein domains and functional insights, Trends in Neuroscience, 2006, vol. 29, No. 5, pp. 286-293, Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville.
Farrer et al, LRRK2 mutations in Parkinson disease, Neurology, 2005, 738-740, 65, AAN Enterprises, Inc.
Biskup et al, Localization of LRRK2 to Membranous and Vesicular Structures in Mammalian Brain, American Neurological Association, 2006, 557-569, 60.
Pearson et al, Structure of the ERM Protein Moesin Reveals the FERM Domain Fold Masked by an Extended Actin Binding Tail Domain, Cell, 2000, 259-270, vol. 101, Cell Press.
Bretscher et al, ERM Proteins and Merlin: Integrators at the Cell Cortex, Mol. Cell. Bio., 2002, 586-599, vol. 3, Nature Publishing Group.
Bosgraaf et al, Roc, a Ras/GTPase domain in complex proteins, Science Direct, 2003, 5-10, Elsevier.
MacLeod et al, The Familial Parkinsonism Gene LRRK2 Regulates Neurite Process Morphology, Neuron, 2006, 587-593, 52, Elsevier Inc.
Troiani et al, Searching for Biomarkers of Aurora-A Kinase Activity: Identification of in Vitro Substrates through a Modified KESTREL Approach, Journal of Proteome Research, 2005, 1296-1303, 4, American Chemical Society.
Campbell et al, Identification of Protein Phosphorylation Sites by a Combination of Mass Spectrometry and Solid Phase Edman Sequencing, Journal of Biomolecular Techniques, 2002, 121-132, vol. 13, Issue 3, MRC Protein Phosphorylation Unit, University of Dundee, Scotland.
Durocher et al, High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells, Nucleic Acids Research, 2002, e9, vol. 30, No. 2, Oxford University Press.
Manning et al, The Protein Kinase Complement of the Human Genome, Science, 2002, 1912-1934, vol. 298.
Zabetian et al, A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations, Neurology, 2005, 741-744, 65, AAN Enterprises, Inc.
Farrer et al, LRRK2 mutations in Parkinson disease, Neurology, 738-740, 65, AAN Enterprises, Inc., 2005.
Zimprich et al, Mutations in LRRK2 Cause Autosomal-Dominant Prkinsonism with Pleomorphic Pathology, Neuron, 2004, 601-607, vol. 44, Cell Press.
Paisan-Ruiz et al, Cloning of the Gene Containing Mutations that Cause PARK8-Linked Parkinson's Disease, Neuron, 2004, 595-600, vol. 44, Cell Press.
Boudeau et al, Emerging roles of pseudokinases, Trends in Cell Biology, vol. 16, No. 9, 443-452 MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, United Kingdom, 2006.
Katayama S et al. “Antisense transcription in the mammalian transcriptome” Science 309:1564-1566, 2005.

Affiliated with

Also associated with

Rating

Methods does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2631265