Human G-coupled protein receptor kinases and polynucleotides...

Details Human G-coupled protein receptor kinases and polynucleotides... Human G-coupled protein receptor kinases and polynucleotides...

2001-03-08

2002-09-03

Achutamurthy, Ponnathapu (Department: 1652)

Chemistry: molecular biology and microbiology

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

Transferase other than ribonuclease

C536S023200, C435S015000, C435S325000, C435S252300, C435S320100

Reexamination Certificate

active

06444456

ABSTRACT:

1. INTRODUCTION
The present invention relates to the discovery, identification, and characterization of novel human polynucleotides encoding proteins that share sequence similarity with animal kinases. The invention encompasses the described polynucleotides, host cell expression systems, the encoded proteins, fusion proteins, polypeptides and peptides, antibodies to the encoded proteins and peptides, and genetically engineered animals that either lack or over express the disclosed polynucleotides, antagonists and agonists of the proteins, and other compounds that modulate the expression or activity of the proteins encoded by the disclosed polynucleotides that can be used for diagnosis, drug screening, clinical trial monitoring and the treatment of diseases and physiological disorders.
2. BACKGROUND OF THE INVENTION
Kinases mediate phosphorylation of a wide variety of proteins and compounds in the cell. In conjunction with phosphatases, kinases are involved in a range of regulatory and signaling pathways. Given the physiological importance of kinases, they have been subject to intense scrutiny and are proven drug targets.
3. SUMMARY OF THE INVENTION
The present invention relates to the discovery, identification, and characterization of nucleotides that encode novel human proteins and the corresponding amino acid sequences of these proteins. The novel human proteins (NHPs) described for the first time herein share structural similarity with animal kinases, including, but not limited to G-protein coupled receptor kinases (GRKs). As such, the novel polynucleotides encode novel GRKs having homologues and orthologs across a range of phyla and species.
The novel human polynucleotides described herein, encode open reading frames (ORFs) encoding proteins of 553 and 353 amino acids in length (see SEQ ID NOS:2 and 4 respectively).
The invention also encompasses agonists and antagonists of the described NHPs, including small molecules, large molecules, mutant NHPs, or portions thereof, that compete with native NHP, peptides, and antibodies, as well as nucleotide sequences that can be used to inhibit the expression of the described NHPs (e.g., antisense and ribozyme molecules, and gene or regulatory sequence replacement constructs) or to enhance the expression of the described NHP polynucleotides (e.g., expression constructs that place the described polynucleotide under the control of a strong promoter system), and transgenic animals that express a NHP transgene, or “knock-outs” (which can be conditional) that do not express a functional NHP. Knock-out mice can be produced in several ways, one of which involves the use of mouse embryonic stem cells (“ES cells”) lines that contain gene trap mutations in a murine homolog of at least one of the described NHPs. When the unique NHP sequences described in SEQ ID NOS:1-5 are “knocked-out” they provide a method of identifying phenotypic expression of the particular gene as well as a method of assigning function to previously unknown genes. Additionally, the unique NHP sequences described in SEQ ID NOS:1-5 are useful for the identification of coding sequence and the mapping a unique gene to a particular chromosome.
Further, the present invention also relates to processes for identifying compounds that modulate, i.e., act as agonists or antagonists, of NHP expression and/or NHP activity that utilize purified preparations of the described NHPs and/or NHP product, or cells expressing the same. Such compounds can be used as therapeutic agents for the treatment of any of a wide variety of symptoms associated with biological disorders or imbalances
4. DESCRIPTION OF THE SEQUENCE LISTING AND FIGURES
The Sequence Listing provides the sequence of the novel human ORFs encoding the described novel human kinase proteins. SEQ ID NO:5 describes a full length ORF and flanking regions.


REFERENCES:
patent: 4215051 (1980-07-01), Schroeder et al.
patent: 4376110 (1983-03-01), David et al.
patent: 4594595 (1986-06-01), Struckman
patent: 4631211 (1986-12-01), Houghten
patent: 4689405 (1987-08-01), Frank et al.
patent: 4713326 (1987-12-01), Dattagupta et al.
patent: 4946778 (1990-08-01), Ladner et al.
patent: 5252743 (1993-10-01), Barrett et al.
patent: 5424186 (1995-06-01), Fodor et al.
patent: 5445934 (1995-08-01), Fodor et al.
patent: 5459127 (1995-10-01), Felgner et al.
patent: 5532151 (1996-07-01), Chantry et al.
patent: 5556752 (1996-09-01), Lockhart et al.
patent: 5591618 (1997-01-01), Chantry et al.
patent: 5700637 (1997-12-01), Southern
patent: 5744305 (1998-04-01), Fodor et al.
patent: 5830721 (1998-11-01), Stemmer et al.
patent: 5837458 (1998-11-01), Minshull et al.
patent: 5869336 (1999-02-01), Meyer et al.
patent: 5877397 (1999-03-01), Lonberg et al.
patent: 5948767 (1999-09-01), Scheule et al.
patent: 6075181 (2000-06-01), Kucherlapati et al.
patent: 6110490 (2000-08-01), Thierry
patent: 6150584 (2000-11-01), Kucherlapati et al.
patent: 6331423 (2001-12-01), Guegler et al.
patent: WO 01/38503 (2001-05-01), None
Broun et al., Science 282:1315-1317, 1998.*
Van de Loo et al., Proc. Natl. Acad. Sci. 92:6743-6747, 1995.*
Weiss et al., GenEMBL accession No. AF063016, Dec. 1998.*
Weiss et al., SPTREMBL accession No. Q9Z2G7, May 1999.*
Database EMBL (Online) May 7, 2000, Birren, B. et al. “Homo sapiens chromosome 17, clone RP11-144C9”, Database accession No. AC068693, XP002181811.
Weiss, Ellen R. et al., “The cloning of GRK7, a candidate cone opsin kinase, from cone and rod-dominant mammalian retinas,” Molecular Vison, vol. 4, Dec. 8, 1998, p. 27, XP002181808.
Premont, Richard T. et al., “The GRK4 subfamily o9f G protein-coupled receptor kinases: Alternative splicing, gene organization, and sequence conservation,” Journal of Biological Chemistry, vol. 274, No. 41, Oct. 8, 1999, pp. 29381-29389, XP002181809.
Benovic, Jeffrey L. et al., “Molecular cloning and expression of GRK6: A new member of the G protein-coupled receptor kinase family,” Journal of Biological Chemistry, vol. 268, No. 26, 1993, pp. 19521-19527, XP002181810.
International Search Report, International Application No. PCT/US01/07500, Nov. 8, 2001.
Bird et al, 1988, “Single-Chain Antigen-Binding Proteins”, Science 242:423-426.
Bitter et al, 1987, “Expression and Secretion Vectors for Yeast”, Methods in Enzymology 153:516-544.
Colbere-Garapin et al, 1981, “A New Dominant Hybrid Selective Marker for Higher Eukaryotic Cells”, J. Mol. Biol. 150:1-14.
Gautier et al, 1987, “&agr;-DNA IV:&agr;-anomeric and &bgr;-anomeric tetrathymidylates covalently linked to intercalating oxazolopyridocarbazole. Synthesis, physiochemical properties and poly (rA) binding”, Nucleic Acids Research 15(16):6625-6641.
Greenspan et al, 1993, “Idiotypes: structure and immunogenicity”, FASEB Journal 7:437-444.
Huse et al, 1989, “Generation of a Large Combinatorial Library of the Immunoglobulin Repertoire in Phage Lambda”, Science 246:1275-1281.
Huston et al, 1988, “Protein engineering of antibody binding sites: Recovery of specific activity in an anti-digoxin single-chain Fv analogue produced inescherichia coli”, Proc. Natl. Acad. Sci. USA 85:5879-5883.
Inoue et al, 1987, “Sequence-dependent hydrolysis of RNA using modified oligonucleotide splints and R Nase H”, FEBS Letters 215(2):327-330.
Inoue et al, 1987, “Synthesis and hybridization studies on two complementary nona(2′-O-methyl)ribonucleotides”, Nucleic Acids Research 15(15):6131-6149.
Inouye & Inouye, 1985, “Up-promoter mutations in the lpp gene ofEscherichia coli”, Nucleic Acids Research 13(9):3101-3110.
Janknecht et al, 1991, “Rapid and efficient purification of native histidine-tagged protein expressed by recombinant vaccinia virus”, PNAS 88:8972-8976.
Kohler & Milstein, 1975, “Continuous cultures of fused cells secreting antibody of predefined specificity”, Nature 256:495-497.
Logan et al, 1984, “Adenovirus tripartite leader sequence enhances translation of mRNAs late after infection”, Proc. Natl. Acad. Sci. USA 81:3655-3659.
Lowy et al, 1980, “Isolation of Transforming DNA: Cloning the Hamster aprt Gene”, Cell 22:817-823.
Morrison et al, 1984, “Chimeric human ant

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