Molecules of the HKID-1-related protein family and uses thereof

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

Reexamination Certificate

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C435S183000, C435S069100, C435S091100, C435S252300, C435S320100, C435S325000, C435S015000, C536S063000

Reexamination Certificate

active

06383791

ABSTRACT:

BACKGROUND OF THE INVENTION
Protein kinases play critical roles in the regulation of biochemical and morphological changes associated with cellular growth and division (D'Urso, G. et al. (1990)
Science
250: 786-791; Birchmeier. C. et al. (1993)
Bioessays
15: 185-189). They serve as growth factor receptors and signal transducers and have been implicated in cellular transformation and malignancy (Hunter, T. et al. (1992)
Cell
70: 375-387; Posada, J. et al. (1992)
Mol. Biol. Cell
3: 583-592; Hunter, T. et al. (1994)
Cell
79: 573-582). For example, protein kinases have been shown to participate in the transmission of signals from growth-factor receptors (Sturgill, T. W. et al. (1988)
Nature
344: 715-718; Gomez, N. et al. (1991)
Nature
353: 170-173), control of entry of cells into mitosis (Nurse, P. (1990)
Nature
344: 503-508; Maller, J. L. (1991)
Curr. Opin. Cell Biol
. 3: 269-275) and regulation of actin bundling (Husain-Chishti, A. et al. (1988)
Nature
334: 718-721). Protein kinases can be divided into two main groups based on either amino acid sequence similarity or specificity for either serine/threonine or tyrosine residues. A small number of dual-specificity kinases are structurally like the serine/threonine-specific group. Within the broad classification, kinases can be further sub-divided into families whose members share a higher degree of catalytic domain amino acid sequence identity and also have similar biochemical properties. Most protein kinase family members also share structural features outside the kinase domain that reflect their particular cellular roles. These include regulatory domains that control kinase activity or interaction with other proteins (Hanks, S. K. et al. (1988)
Science
241: 42-52). Rat KID-1 is a serine/threonine protein kinase that is induced by membrane depolarization or forskolin but not by neurotrophins or growth factors (Feldman, J. D. et al. (1998).
J. Biol. Chem
. 273:16535-16543). Rat KID-1 is induced in specific regions of the hippocampus and cortex in response to kainic acid and electroconvulsive shock, suggesting that rat KID-1 is involved in neuronal function, synaptic plasticity, learning, and memory as well as kainic acid seizures and some nervous system-related diseases such as seizures and epilepsy. Rat KID-1 paralogs include the PIM-1 proteins known to be proto-oncogenes. The present invention is based, at least in part, on the discovery of the human species ortholog of rat KID-1, termed HKID-1.
SUMMARY OF THE INVENTION
The present invention is based, at least in part, on the discovery of a gene encoding HKID-1, an intracellular protein that is predicted to be a member of the serine/threonine protein kinase superfamily. Based on this, the present invention provides isolated HKID-1 proteins and nucleic acid molecules encoding HKID-1 proteins. The present invention also provides methods of detecting HKID-1 protein or HKID-1 nucleic acids and methods for identifying modulators of HKID-1 protein or HKID-1 nucleic acids.

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