Novel kinases and uses thereof

Abstract

Novel kinase polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length kinase proteins, the invention further provides isolated kinase fusion proteins, antigenic peptides, and anti-kinase antibodies. The invention also provides kinase 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 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 90% identical to the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:1 1, SEQ ID NO:13, 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, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, or a complement thereof;   c) a nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14;   d) a nucleic acid molecule which encodes a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO: 14; 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, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, or a complement thereof under conditions of hybridization in 6×SSC at 42° C., followed by washing with 1×SSC at 55° C.   
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , which is selected from the group consisting of:
 a) a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1 SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, or a complement thereof; and   b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14.   
     
     
         3 . The nucleic acid molecule of  claim 1  further comprising vector nucleic acid sequences. 
     
     
         4 . The nucleic acid molecule of  claim 1  further comprising nucleic acid sequences encoding a heterologous polypeptide. 
     
     
         5 . A host cell which contains the nucleic acid molecule of  claim 1 . 
     
     
         6 . An isolated polypeptide selected from the group consisting of:
 (a) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14;   b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, or a complement thereof under conditions of hybridization in 6×SSC at 42° C., followed by washing with 1×SSC at 55° C.;   c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, or a complement thereof; and   d) a polypeptide comprising an amino acid sequence which is at least 90% identical to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14.   
     
     
         7 . The isolated polypeptide of  claim 6  comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14. 
     
     
         8 . The polypeptide of  claim 6  further comprising heterologous amino acid sequences. 
     
     
         9 . An antibody which selectively binds to a polypeptide of  claim 6 . 
     
     
         10 . A method for producing a polypeptide selected from the group consisting of:
 (a) a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO: 14;   b) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14; and   c) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, or SEQ ID NO:14, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, or a complement thereof under conditions of hybridization in 6×SSC at 42° C., followed by washing with 1×SSC at 55° C.;   
       comprising culturing the host cell of  claim 5  under conditions in which the nucleic acid molecule is expressed. 
     
     
         11 . A method for detecting the presence of a polypeptide of  claim 6  in a sample, comprising:
 a) contacting the sample with a compound which selectively binds to a polypeptide of  claim 6 ; and 
 b) determining whether the compound binds to the polypeptide in the sample. 
 
     
     
         12 . The method of  claim 11 , wherein the compound which binds to the polypeptide is an antibody. 
     
     
         13 . A kit comprising a compound which selectively binds to a polypeptide of  claim 6  and instructions for use. 
     
     
         14 . 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. 
 
     
     
         15 . The method of  claim 14 , wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe. 
     
     
         16 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use. 
     
     
         17 . A method for identifying a compound which binds to a polypeptide of  claim 6  comprising the steps of:
 a) contacting a polypeptide, or a cell expressing a polypeptide of  claim 6  with a test compound; and 
 b) determining whether the polypeptide binds to the test compound. 
 
     
     
         18 . The method of  claim 17 , 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-mediated signal transduction.   
     
     
         19 . A method for modulating the activity of a polypeptide of  claim 6  comprising contacting a polypeptide or a cell expressing a polypeptide of  claim 6  with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide. 
     
     
         20 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 6 , comprising:
 a) contacting a polypeptide of  claim 6  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.