MEKK1 molecules and uses thereof

Abstract

The invention provides full-length, human isolated nucleic acids molecules, designated MEKK1 nucleic acid molecules, which encode a MEKK family member. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing MEKK1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a MEKK1 gene has been introduced or disrupted. The invention still further provides isolated MEKK1 proteins, fusion proteins, antigenic peptides and anti-MEKK1 antibodies. Diagnostic 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 the nucleotide sequence which is at least 90% identical to the nucleotide sequence of SEQ ID NO:1 or the cDNA insert of the plasmid deposited with the ATCC as Accession Number PTA-1836; and    b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number PTA-1836.    
     
     
         2 . The nucleic acid molecule of  claim 1  further comprising vector nucleic acid sequences.  
     
     
         3 . The nucleic acid molecule of  claim 1  further comprising nucleic acid sequences encoding a heterologous polypeptide.  
     
     
         4 . A non-human host cell containing the nucleic acid molecule of  claim 1 .  
     
     
         5 . An isolated polypeptide selected from the group consisting of: 
 a) a polypeptide comprising an amino acid sequence which is encoded by a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1 or nucleotides 7-4545 of SEQ ID NO:1;    b) a polypeptide comprising an amino acid sequence which is encoded by a nucleic acid comprising the nucleotide sequence of the cDNA insert of the plasmid deposited with the ATCC as Accession Number PTA-1836 or a portion thereof, comprising the coding region;    c) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein said fragment comprises at least 500 contiguous amino acids of SEQ ID NO:2 and has MEKK1 activity;    d) a polypeptide comprising an amino acid sequence which is encoded by a nucleic acid which has at least 90% nucleotide sequence identity with the entire length of the nucleotide sequence of SEQ ID NO:1, wherein said nucleic acid comprises nucleotide residues 1 to 64 of SEQ ID NO:1 and wherein said polypeptide has MEKK1 activity;    e) a polypeptide comprising an amino acid sequence which is encoded by a nucleic acid which has at least 90% nucleotide sequence identity with the entire length of the nucleotide sequence of the insert of the plasmid deposited with the ATCC as Accession Number PTA-1836, wherein said nucleic acid comprises nucleotide residues 1 to 64 of SEQ ID NO:1 and wherein said polypeptide has MEKK1 activity;    f) a polypeptide comprising the amino acid sequence of SEQ ID NO:2 or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-1836;    g) a polypeptide comprising a MEKK1 variant, wherein said MEKK1 variant comprises an amino acid sequence has at least 90% amino acid sequence identity with the entire length of SEQ ID NO:2, wherein said MEKK1 variant has amino acid residues 1 to 20 of SEQ ID NO:2, and wherein said MEKK1 variant has MEKK1 activity; and    h) a polypeptide comprising a MEKK1 variant, wherein said MEKK1 variant comprises an amino acid sequence having at least 98% amino acid sequence identity with the entire length of SEQ ID NO:2 and wherein said variant has MEKK1 activity.    
     
     
         6 . The isolated polypeptide of  claim 5  selected from the group consisting of: 
 a) a polypeptide comprising the amino acid sequence of SEQ ID NO:2; and    b) a polypeptide comprising the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Accession Number PTA-1836.    
     
     
         7 . The polypeptide of  claim 5  further comprising heterologous amino acid sequences.  
     
     
         8 . The polypeptide of  claim 5  further comprising a detectable label.  
     
     
         9 . An antibody which selectively binds to a polypeptide of  claim 5 .  
     
     
         10 . A method for producing a polypeptide comprising the amino acid sequence of SEQ ID NO:2 or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Accession Number PTA-1836; 
 comprising culturing the host cell of  claim 4  under conditions in which the nucleic acid molecule is expressed.    
     
     
         11 . A method for detecting the presence of a polypeptide of  claim 5  in a sample, comprising: 
 a) contacting the sample with a compound which selectively binds to a polypeptide of  claim 5;  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 5  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 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use.  
     
     
         16 . A method for identifying a compound which binds to a polypeptide of  claim 5  comprising the steps of: 
 a) contacting a polypeptide, or a cell expressing a polypeptide of  claim 5  with a test compound; and    b) determining whether the polypeptide binds to the test compound.    
     
     
         17 . The method of  claim 16 , 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 MEKK1-mediated signal transduction.    
     
     
         18 . A method for modulating the activity of a polypeptide of  claim 5  comprising contacting a polypeptide or a cell expressing a polypeptide of  claim 5  with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.  
     
     
         19 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 5 , comprising: 
 a) contacting a polypeptide of  claim 5  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.    
     
     
         20 . An isolated polypeptide selected from the group consisting of: 
 a) a polypeptide consisting of the amino acid sequence of SEQ ID NO:2; and    b) a polypeptide consisting of the amino acid sequence encoded by the nucleotide sequence of the insert of the plasmid deposited with the ATCC as Accession Number PTA-1836.