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  Human orthologues of wartUSPTO Application #: 20060292573Title: Human orthologues of wart Abstract: The present invention relates in part to hWART nucleic acid molecules. The invention also relates in part to nucleic acid molecules encoding portions of hWART full-length proteins, nucleic acid vectors containing hWART nucleic acid molecules, recombinant cells containing such nucleic acid vectors, polypeptides purified from such recombinant cells, antibodies to such polypeptides, and methods of identifying compounds that modulate the function of an hWART polypeptide. Also disclosed are methods for diagnosing abnormal cell proliferative conditions in an organism using hWART-related molecules or compounds. (end of abstract) Agent: Foley And Lardner LLP Suite 500 - Washington, DC, US Inventors: Gregory Plowman, Peter Flanagan USPTO Applicaton #: 20060292573 - Class: 435006000 (USPTO) Related Patent Categories: Chemistry: Molecular Biology And Microbiology, Measuring Or Testing Process Involving Enzymes Or Micro-organisms; Composition Or Test Strip Therefore; Processes Of Forming Such Composition Or Test Strip, Involving Nucleic Acid The Patent Description & Claims data below is from USPTO Patent Application 20060292573. Brief Patent Description - Full Patent Description - Patent Application Claims
RELATED APPLICATIONS [0001] This application is related to and claims priority to the U.S. Provisional Application Ser. No. 60/072,023, filed on Jan. 21, 1998, by Plowman et al., and entitled "HUMAN ORTHOLOGUES OF WART" (Lyon & Lyon Docket No. 224/006), which is hereby incorporated by reference herein in its entirety, including any drawings. FIELD OF THE INVENTION [0002] The present invention relates in part to protein kinases. In particular, the invention concerns the identification of protein kinase proteins which are human orthologues of the drosophila WART gene (hWART). BACKGROUND OF THE INVENTION [0003] The following description is provided to aid in understanding the invention, but is not admitted to describe or constitute prior art to the invention. [0004] Cellular signal transduction is a fundamental mechanism whereby extracellular stimuli are relayed to the interior of cells and thereby regulate diverse cellular processes. One of the key biochemical mechanisms of signal transduction involves the reversible phosphorylation of proteins. Phosphorylation of polypeptides regulates the activity of mature proteins by altering their structure and function. Phosphate most often resides on the hydroxyl moiety of serine, threonine, or tyrosine amino acids in proteins. [0005] Enzymes that mediate phosphorylation of cellular effectors generally fall into two classes. The first class consists of protein kinases which transfer a phosphate moiety from nucleotide triposphates to protein substrates. The second class consists of protein phosphatases which hydrolyze phosphate moieties from phosphoryl protein substrates. The converse functions of protein kinases and protein phosphatases balance and regulate the flow of signals in signal transduction processes. [0006] Protein kinases are generally divided into two classes: receptor and non-receptor type proteins. Protein kinases may also be divided into three classes based upon the amino acids they act upon: (1) Some catalyze the addition or hydrolysis of phosphate on serine or threonine only; (2) some catalyze the addition or hydrolysis of phosphate on tyrosine only; and (3) some catalyze the addition or hydrolysis of phosphate on serine, threonine, and tyrosine. [0007] Altered protein kinase activity has been associated with multiple abnormal cellular functions, including increased cell proliferation. Increased cell proliferation can result from at least two cellular events: (i) mutation, chromosome translocation, or gene amplification of proto-oncogenes (Bishop, Cell 64:235-248, 1991), or (ii) inactivation, loss by mutation, chromosomal loss, mitotic recombination, or gene conversion of tumor suppressor genes (Lasko et al., Ann Rev Genet 25:281-314). [0008] A large number of potential tumor suppressor genes have been isolated from Drosophila melanogaster, a species of fruit fly. Watson et al., J. Cell Sci. 18:19-33, 1994. Potential tumor suppressor genes are identified in this organism by first deleting, obstructing, or mutating a gene, and then detecting over-proliferative cell growth of specific tissues in dissected larvae and pupae. Xu et al., Development 121:1053-1063, 1995. This organism provides an ideal system for identifying potential tumor suppressor genes as it reproduces rapidly and its genome is readily manipulated by persons skilled in the art. [0009] An example of a putative tumor suppressor gene identified in Drosophila is the wts gene. Loss or inactivation of both copies of the wts gene results in the growth of tumors on the legs and wings of the flies. Bryant et al., Development 1993 Supplement: 239-249, 1993. The large size of these tumors suggests that the cells undergo more divisions than normal. Id. In addition, the rounded shape of the tumors suggests that the division of the mutant cells is not preferentially oriented. Id. These observations taken together with the increased thickness of the cuticles around the mutant cells suggest that the wts gene regulates cell adhesion, cell contact inhibition, and/or cell boundary recognition in Drosophila. [0010] Several of the genes characterized as potential tumor suppressors in Drosophila are cloned. In particular, the wts gene contains a region that bears sequence similarity to the catalytic regions of mammalian non-receptor serine/threonine protein kinases. Watson, BioEssays 17:673-676, 1995. However, the human orthologues of the drosophila wts gene have not been reported. SUMMARY OF THE INVENTION [0011] The invention relates in part to novel human orthologues of the Drosophila wts gene (hWARTs). The Drosophila wts gene encodes a non-receptor serine/threonine kinase. The properties of the human orthologues are described herein. The present invention concerns polypeptides of hWART, nucleic acids encoding such polypeptides, cells, tissues and animals containing such nucleic acids, antibodies to the polypeptides, assays utilizing the polypeptides, and methods relating to all of the foregoing. [0012] The term "orthologue" as used herein, refers to a gene that is more closely related, in terms of nucleic acid sequence, to another gene than a gene which is a homologue. In the context of this invention, "homologous" indicates that the nucleotide sequences of two genes and/or the sequences of the gene products (e.g., amino acid sequences) have significant similarity, and that the gene products perform a similar cellular function. Thus, two homologous genes may have sequences which have 50, 60, 70, 80, 90, or greater percent nucleotide sequence identity. By "closely related" in the context of this invention, it is meant nucleic acid sequences that have greater than 90% identity. [0013] The hWARTS genes encode proteins that are potential drug targets for controlling aberrant cell proliferation. Unlike their Drosophila ortholog, the hWARTS genes may not function as tumor suppressor genes. While their mRNA is absent from most normal cells they are abundantly expressed in many types of tumor cells. However, based on the high degree of sequence identity in the catalytic and non-catalytic regions between the hWART proteins and the Drosophila wts, it is likely that the hWART genes are involved in regulating cell adhesion, cell contact inhibition, and/or cell boundary recognition, and in regulation of signal transduction pathways related to cell proliferation. [0014] Thus, in a first aspect, the invention features an isolated, enriched, or purified nucleic acid molecule encoding an hWART polypeptide. [0015] By "isolated" in reference to nucleic acid it is meant a polymer of 14, 17, 21 or more nucleotides conjugated to each other, including DNA or RNA that is isolated from a natural source or that is synthesized. The isolated nucleic acid of the present invention is unique in the sense that it is not found in a pure or separated state in nature. Use of the term "isolated" indicates that a naturally occurring sequence has been removed from its normal cellular (i.e., chromosomal) environment. Thus, the sequence may be in a cell-free solution or placed in a different cellular environment. The term does not imply that the sequence is the only nucleotide sequence present, but that it is essentially free (about 90-95% pure at. least) of non-nucleotide material naturally associated with it and thus is meant to be distinguished from isolated chromosomes. [0016] By the use of the term "enriched" in reference to nucleic acid it is meant that the specific DNA or RNA sequence constitutes a significantly higher fraction (2-5 fold) of the total DNA or RNA present in the cells or solution of interest than in normal or diseased cells or in the cells from which the sequence was taken. This could be caused by a person by preferential reduction in the amount of other DNA or RNA present, or by a preferential increase in the amount of the specific DNA or RNA sequence, or by a combination of the two. However, it should be noted that "enriched" does not imply that there are no other DNA or RNA sequences present, just that the relative amount of the sequence of interest has been significantly increased. [0017] The term "significant" here is used to indicate that the level of increase is useful to the person making such an increase, and generally means an increase relative to other nucleic acids of about at least 2 fold, more preferably at least 5 to 10 fold or even more. The term also does not imply that there is no DNA or RNA from other sources. The other source DNA may, for example, comprise DNA from a yeast or bacterial genome, or a cloning vector such as pUC19. This term distinguishes the sequence from naturally occurring enrichment events, such as viral infection, or tumor type growths, in which the level of one mRNA may be naturally increased relative to other species of mRNA. That is, the term is meant to cover only those situations in which a person has intervened to elevate the proportion of the desired nucleic acid. [0018] It is also advantageous for some purposes that a nucleotide sequence be in purified form. The term "purified" in reference to nucleic acid does not require absolute purity (such as a homogeneous preparation); instead, it represents an indication that the sequence is relatively purer than in the natural environment (compared to the natural level this level should be at least 2-5 fold greater, e.g., in terms of mg/ml). Individual clones isolated from a cDNA library may be purified to electrophoretic homogeneity. The claimed DNA molecules obtained from these clones can be obtained directly from total DNA or from total RNA. The cDNA clones are not naturally occurring, but rather are preferably obtained via manipulation of a partially purified naturally occurring substance (messenger RNA). The construction of a cDNA library from mRNA involves the creation of a synthetic substance (cDNA) and pure individual cDNA clones can be isolated from the synthetic library by clonal selection of the cells carrying the cDNA library. Thus, the process which includes the construction of a cDNA library from mRNA and isolation of distinct cDNA clones yields an approximately 10.sup.6-fold purification of the native message. Thus, purification of at least one order of magnitude, preferably two or three orders, and more preferably four or five orders of magnitude is expressly contemplated. The term is also chosen to distinguish clones already in existence which may encode hWARTs but which have not been isolated from other clones in a library of clones. Thus, the term covers clones encoding hWART which are isolated from other non-hWART clones. [0019] The term "nucleic acid molecule" describes a polymer of deoxyribonucleotides (DNA) or ribonucleotides (RNA) The nucleic acid molecule may be isolated from a natural source by cDNA cloning or subtractive hybridization or synthesized manually. The nucleic acid molecule may be synthesized manually by the triester synthetic method or by using an automated DNA synthesizer. [0020] The term "cDNA cloning" refers to hybridizing a small nucleic acid molecule, a probe, to genomic cDNA. The probe hybridizes (binds) to complementary sequences of cDNA. Continue reading... Full patent description for Human orthologues of wart Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Human orthologues of wart patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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