12832, a novel human kinase-like molecule and uses thereof

Abstract

Novel human kinase-like polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length kinase-like proteins, the invention further provides isolated kinase-like fusion proteins, antigenic peptides, and anti-kinase-like antibodies. The invention also provides kinase-like nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a kinase-like gene has been introduced or disrupted. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

1 . An isolated nucleic acid molecule selected from the group consisting of: 
 a) a nucleic acid molecule comprising a nucleotide sequence which is at least 45% identical to the nucleotide sequence of SEQ ID NO:1, the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-2342, or a complement thereof;    b) a nucleic acid molecule comprising a fragment of at least 15 nucleotides of the nucleotide sequence of SEQ ID NO:1, the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-2342, or a complement thereof;    c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2, or an amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-2342;    d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, or an amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-2342, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2, or the polypeptide encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-2342; and    e) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, or an amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-2342, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, or a complement thereof under stringent conditions.    
     
     
         2 . An isolated polypeptide selected from the group consisting of: 
 (a) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, or an amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-2342, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2, or an amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-2342;    b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, or an amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-2342, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, or a complement thereof under stringent conditions; and    c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 45% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1, or a complement thereof.    
     
     
         3 . An antibody which selectively binds to a polypeptide of  claim 2 .  
     
     
         4 . A method for detecting the presence of a polypeptide of  claim 2  in a sample, comprising: 
 a) contacting the sample with a compound which selectively binds to a polypeptide of  claim 2;  and    b) determining whether the compound binds to the polypeptide in the sample.    
     
     
         5 . The method of  claim 4 , wherein the compound which binds to the polypeptide is an antibody.  
     
     
         6 . A kit comprising a compound which selectively binds to a polypeptide of  claim 2  and instructions for use.  
     
     
         7 . A method for detecting the presence of a nucleic acid molecule of  claim 1  in a sample, comprising the steps of: 
 a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and    b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample.    
     
     
         8 . The method of  claim 7 , wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.  
     
     
         9 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use.  
     
     
         10 . A method for identifying a compound which binds to a polypeptide of  claim 2  comprising the steps of: 
 a) contacting a polypeptide, or a cell expressing a polypeptide of  claim 2  with a test compound; and    b) determining whether the polypeptide binds to the test compound.    
     
     
         11 . The method of  claim 10 , wherein the binding of the test compound to the polypeptide is detected by a method selected from the group consisting of: 
 a) detection of binding by direct detecting of test compound/polypeptide binding;    b) detection of binding using a competition binding assay;    c) detection of binding using an assay for kinase-like-mediated signal transduction.    
     
     
         12 . A method for modulating the activity of a polypeptide of  claim 2  comprising contacting a polypeptide or a cell expressing a polypeptide of  claim 2  with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.  
     
     
         13 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 2 , comprising: 
 a) contacting a polypeptide of  claim 2  with a test compound; and    b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound which modulates the activity of the polypeptide.    
     
     
         14 . A method for treating cancer in a patient, comprising introducing into the vicinity of the cancer in the patient a compound which modulates the activity of a polypeptide of  claim 2 .  
     
     
         15 . The method of  claim 14 , wherein the cancer is located in selected from the group consisting of: lung tissue, breast tissue, and colon tissue.  
     
     
         16 . A method of delivering a chemotherapeutic agent to a vertebrate cancer cell which is abnormally expressing a kinase-like molecule, wherein said method comprises contacting the cell with an antibody or biologically active antibody fragment a polypeptide of  claim 2 .  
     
     
         17 . The method of  claim 16 , wherein said cancer cell is in the breast, colon, or lung.  
     
     
         18 . A method of treating lung or breast or colon cancer in a patient, comprising introducing into the vicinity of the cancer in the patient compound which modulates the activity of a polypeptide of  claim 2 .  
     
     
         19 . A method of treating a pre-neoplastic or neoplastic disease characterized by abnormal expression of a kinase-like molecule in a patient comprising administering to said patient a therapeutically effective amount of a composition comprising a compound which modulates the activity of a polypeptide of  claim 2 .  
     
     
         20 . A method of delivering a chemotherapeutic agent to a vertebrate cancer cell which is abnormally expressing a kinase-like molecule said method comprising contacting the cell with an antibody or biologically active antibody fragment which specifically binds a polypeptide of  claim 2.