Regulation of neuronal function through metabotropic...

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Transferase other than ribonuclease

Reexamination Certificate

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C435S184000

Reexamination Certificate

active

07129073

ABSTRACT:
The present invention provides methods and compositions for modulating the activities of metabotropic glutamate receptor intracellular signaling molecules. The present invention provides methods and compositions for modulating the activities of casein kinase I and/or cyclin-dependent kinase 5 in cells or tissues. The present invention provides methods of modulating the function of calcium channels in cells or tissues. The present invention provides methods of treating calcium channel dysfunction. The present invention provides methods of identifying agents that modulate the activities of the metabotropic glutamate receptor intracellular signaling molecules casein kinase I and/or cyclin-dependent kinase 5 for use in such treatments.

REFERENCES:
patent: PCT/US02/19288 (2002-06-01), None
Sharma, P et al. Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation. Proc. Natl. Acad. Sci. USA. 1999. 96: 11156-11160.
Gietzen, KF et al. Identification of inhibitory autophosphorylation sites in casein kinase I e. Journal of Biological Chemistry. 1999. 274(45): 32063-32070.
Hernandez-Lopez, S et al. D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLC beta1-IP3-calcineurin-signaling cascade. Journal of Neuroscience. Dec. 2000. 20(24): 8987-8995.
Nath et al., “Processing of cdk5 Activator p35 to Its Truncated Form (p25) by Calpain in Acutely Injured Neuronal Cells”, Jun. 5, 2000, Biochemical and Biophysical Research Communications, pp. 16-21.
Cegielska et al., “Autoinhibition of Casein Kinase I ε (CKIε) Is Relieved by Protein Phosphatases and Limited Proteolysis”, Sep. 3, 1997, The Journal of Biological Chemistry, vol. 273, pp. 1357-1364.
Desdouits et al., “Phosphorylation of DARPP-32, a Dopamine- and cAMP-regulated Phosphoprotein, by Casein Kinase I in Vitro and in Vivo”, Oct. 31, 1994, Journal of Biological Chemistry, vol. 270, No. 15 pp. 8772-8778.
Liu et al., “Regulation of cyclin-dependent kinase 5 and casein kinase 1 by metabotropic glutamate receptors”, Sep. 25, 2001, PNAS, vol. 98, pp. 11062-11068.
SIGMA-RBI Handbook of Receptor Classification and Signal Transduction(4thedition; K.J. Watling, editor; Sigma-RBI, Natick MA, 2001), pp. 194-195.

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