Human serum inducible kinase (Snk)

Details Human serum inducible kinase (Snk) Human serum inducible kinase (Snk)

2000-02-16

2001-06-12

Prouty, Rebecca E. (Department: 1652)

Chemistry: molecular biology and microbiology

Enzyme , proenzyme; compositions thereof; process for...

Transferase other than ribonuclease

C530S350000

Reexamination Certificate

active

06245544

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to newly identified polypeptides and polynucleotides encoding such polypeptides, to their use in therapy and in identifying compounds which may be agonists, antagonists and/or inhibitors which are potentially useful in therapy, and to production of such polypeptides and polynucleotides.
BACKGROUND OF THE INVENTION
The drug discovery process is currently undergoing a fundamental revolution as it embraces ‘functional genomics’, that is, high throughput genome- or gene-based biology. This approach is rapidly superseding earlier approaches based on ‘positional cloning’. A phenotype, that is a biological function or genetic disease, would be identified and this would then be tracked back to the responsible gene, based on its genetic map position.
Functional genomics relies heavily on the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available. There is a continuing need to identify and characterise further genes and their related polypeptides/proteins, as targets for drug discovery.
Protein phosphorylation plays a critical role in promoting cell cycle progression. Most prominent among the regulators of the cell cycle is a family of cyclins, cyclin dependent kinases (CDKs), CDK regulatory kinases, and phosphatases (See Lees, E., Curr. Opin. Cell Biol. 1995, 7:773-780; Piwinica-Worms, H., J. Lab. Clin. Med. 1996, 128:350-354). A new family of cell cycle regulators, the polo-like kinases, has been identified and shown to be essential for progression through the cell cycle (Lane, H. A., Trends in Cell Biol. 1997, 7:63-68). This subfamily of serine/threonine kinases contains the following related but distinctmembers: (1) Plk (polo-like kinase; human) and its homologs Polo (Drosophila), cdc5 (
S. cerevisiae
), Plx (Xenopus), and Plo (
S. pombe
); (2) Prk (polo-related kinase; human) and its murine homologFnk; and (3) Snk (serum-inducible kinase; murine). Known functions of these genes include regulation of spindle assembly (human plk1, Drosophila polo,
S. pombe
plo1) and late nuclear division (
S. cerevisiae
cdc5). PLK1 expression correlates with the mitotic index (Holtrich U., Proc. Natl. Acad. Sci. 1994, 91:1736-1740) and mutations of the Drosophila polo or
S. cerevisiae
cdc5 gene cause mitotic arrest. In addition, antibodies directed against human PLK1 cause impaired mitosis. Progression from the G2 phase to the M phase of the cell cycle requires the activity of cdc25 phosphatase. PLX1 (Xenopus) phosphorylates and, thereby, activates cdc25-c, an isoform of cdc25 (Dunphy W. G., Science 1996. 273:1377-1380). The murine Snk is an early growth response gene which reportedly phosphorylates heterologous (although unidentified) substrates (Simmons D. L., Mol. Cell.Biol. 1992, 12:4164-4169). Identification of the consensus sequence of the polo-like family in the amino-terminal putative catalytic domain of Snk (published murine sequence and present invention) and the consensus polo box sequence in the carboxy terminus place this protein in the polo-like family and suggest that this enzyme is potentially a critical regulator of cell cycle progression.
SUMMARY OF THE INVENTION
The present invention relates to Serum Inducible Kinase (Snk), in particular Serum Inducible Kinase (Snk) polypeptides and Serum Inducible Kinase (Snk) polynucleotides, recombinant materials and methods for their production. In another aspect, the invention relates to methods for using such polypeptides and polynucleotides, including the treatment of proliferative diseases such as leukemia, solid tumor cancers and metastases; chronic inflammatory proliferative diseases such as psoriasis and rheumatoid arthritis; proliferative cardiovascular diseases such as restenosis; proliferative ocular disorders such as diabetic retinopathy; and benign hyperproliferative diseases such as hemangiomas, hereinafter referred to as “the Diseases”, amongst others In a further aspect, the invention relates to methods for identifying agonists and antagonists/inhibitors using the materials provided by the invention, and treating conditions associated with Serum Inducible Kinase (Snk) imbalance with the identified compounds In a still further aspect, the invention relates to diagnostic assays for detecting diseases associated with inappropriate Serum Inducible Kinase (Snk) activity or levels.


REFERENCES:
patent: 5885803 (1999-03-01), Bandman et al.
Simmons et al. “Identification of an Early-Growth Response Gene Encoding a Novel Putative Protein Kinase”, Molecular and Cellular Biology, vol. 12 (9), pp. 4164-4169 (1992).
Accession No. AF059617, Apr. 28, 1998.
Watanabe, et al. “Mutation of a single amino acid converts germ cell alkaline phasphatase to placental alkaline phosphatase”, J. Biol. Chem., 1991, 266(31):21171-8 (Abstract).
Lee, et al., “An arginine to glutamine mutation in residue 109 of human ornithine transcarbamylase completely abolishes enzymatic activity in Cos1 cells”, J. Clin Invest, 1989, 84(6):1762-6 (Abstract).
Chaidaroglou, et al., “Function of arginine-166 in the active site ofEscherichia colialkaline phosphatase”, Biochemistry, 1988, 27(22):8338-43 (Abstract).
Simmons et al., Database pir64, Accession No. A44493, 1992.*
Bandman et al., database/geneseq 36, see the alignment, 1999.

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