Cytokine receptor zcytor17

Abstract

Novel polypeptides, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for zcytorl7, a novel cytokine receptor. The polypeptides may be used within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block ligand activity in vitro and in vivo. The polynucleotides encoding zcytorl7, are located on chromosome 5, and can be used to identify a region of the genome associated with human disease states. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

What is claimed is:  
     
         1 . An isolated polypeptide comprising an amino acid sequence having at least 95% sequence identity with amino acid residues 33-662 of SEQ ID NO:54, wherein the polypeptide stimulates inflammation upon binding zcytor17 ligand.  
     
     
         2 . The isolated polypeptide of  claim 1  wherein the polypeptide comprises amino acid residues 1-662 of SEQ ID NO:54.  
     
     
         3 . The isolated polypeptide of  claim 1  wherein the polypeptide consists of amino acid residues 33-662.  
     
     
         4 . An isolated zcytor17 soluble receptor comprising an amino acid sequence having at least 95% sequence identity with amino acid residues 33-532 of SEQ ID NO:54, wherein the zcytor17 soluble receptor reduces zcytor17 ligand induced inflammation.  
     
     
         5 . The isolated zcytor17 soluble receptor of  claim 4  wherein the zcytor17 soluble receptor is fused to a heavy chain constant region of an immunoglobulin.  
     
     
         6 . The isolated zcytor17 soluble receptor of  claim 5  wherein the heavy chain constant region of the immunoglobulin is human Fc4.  
     
     
         7 . An isolated polypeptide comprising amino acid residues 33-662 of SEQ ID NO:54.  
     
     
         8 . The isolated polypeptide of  claim 7  wherein the polypeptide comprises amino acid residues 1-662 of SEQ ID NO:54.  
     
     
         9 . An isolated zcytor17 soluble receptor comprising an amino acid sequence of 33-532 of SEQ ID NO:54.  
     
     
         10 . The isolated zcytor17 soluble receptor of  claim 9  further comprising human immunoglobulin Fc4.  
     
     
         11 . An isolated polynucleotide encoding a polypeptide wherein the encoded polypeptide comprises an amino acid sequence having at least 95% sequence identity with amino acid residues 33-662 of SEQ ID NO:54, wherein the polypeptide stimulates inflammation upon binding zcytor17 ligand.  
     
     
         12 . The isolated polynucleotide of  claim 11  wherein the polypeptide comprises amino acid residues 1-662 of SEQ ID NO:54.  
     
     
         13 . The isolated polynucleotide of  claim 11  wherein the polypeptide consists of amino acid residues 33-662.  
     
     
         14 . An isolated polynucleotide encoding a zcytor17 soluble receptor wherein the encoded zcytor17 soluble receptor comprises an amino acid sequence having at least 95% sequence identity with amino acid residues 33-532 of SEQ ID NO:54, wherein the zcytor17 soluble receptor reduces zcytor17 ligand induced inflammation.  
     
     
         15 . The isolate polynucleotide of  claim 14  wherein the zcytor17 soluble receptor is fused to a heavy chain constant region of an immunoglobulin.  
     
     
         16 . The isolate polynucleotide of  claim 15  wherein the heavy chain constant region of the immunoglobulin is human Fc4.  
     
     
         17 . An isolated polynucleotide encoding a polypeptide wherein the encoded polypeptide comprises amino acid residues 33-662 of SEQ ID NO:54.  
     
     
         18 . An isolated polynucleotide encoding a zcytor17 soluble receptor wherein the encoded zcytor17 soluble receptor comprises an amino acid sequence of 33-532 of SEQ ID NO:54.  
     
     
         19 . A composition comprising: 
 a polypeptide comprising amino acid residues 33-662 of SEQ ID NO:54; and    a pharmaceutically acceptable vehicle.    
     
     
         20 . A composition comprising: 
 a zcytor17 soluble receptor comprising amino acid residues 33-532 of SEQ ID NO:54; and    a pharmaceutically acceptable vehicle.    
     
     
         21 . The composition of  claim 20  wherein the zcytor17 soluble receptor further comprises human immunoglobulin Fc4.  
     
     
         22 . An isolated polynucleotide comprising nucleotides 593-2482 of SEQ ID NO:53.  
     
     
         23 . The isolated polynucleotide of  claim 22  wherein the nucleotides comprise nucleotides 497-2482 of SEQ ID NO:53.  
     
     
         24 . An isolated polynucleotide comprising nucleotides 593-2092 of SEQ ID NO:53.  
     
     
         25 . An expression vector comprising the following operably linked elements: 
 a transcription promoter;    a DNA segment encoding a polypeptide wherein the encoded polypeptide comprises amino acid residues 33-662 of SEQ ID NO:54; and    a transcription terminator,    wherein the promoter is operably linked to the DNA segment, and the DNA segment is operably linked to the transcription terminator.    
     
     
         26 . The expression vector of  claim 25  further comprising a secretory signal sequence operably linked to the DNA segment.  
     
     
         27 . The expression vector of  claim 26  wherein the secretory signal sequence encodes a polypeptide comprising amino acid residues 1-32 of SEQ ID NO:54.  
     
     
         28 . An expression vector comprising the following operably linked elements: 
 a transcription promoter;    a DNA segment encoding a zcytor17 soluble receptor wherein the encoded zcytor17 soluble receptor comprises amino acid residues 33-532 of SEQ ID NO:54; and    a transcription terminator,    wherein the promoter is operably linked to the DNA segment, and the DNA segment is operably linked to the transcription terminator.    
     
     
         29 . The expression vector of  claim 28  further comprising a secretory signal sequence operably linked to the DNA segment.  
     
     
         30 . The expression vector of  claim 29  wherein the secretory signal sequence encodes a polypeptide comprising amino acid residues 1-32 of SEQ ID NO:54.  
     
     
         31 . The expression vector of  claim 28  further comprising a human immunoglobulin Fc4 operably linked to the DNA segment.  
     
     
         32 . A cultured cell comprising the expression vector of  claim 25 , wherein the cell expresses the polypeptide encoded by the DNA segment.  
     
     
         33 . A cultured cell comprising the expression vector of  claim 28 , wherein the cell expresses the zcytor17 soluble receptor encoded by the DNA segment.  
     
     
         34 . A DNA construct encoding a fusion protein, the DNA construct comprising: 
 a first DNA segment encoding a polypeptide wherein the encoded polypeptide comprises an amino acid sequence 33-662 of SEQ ID NO:54;    at least one other DNA segment encoding an additional polypeptide;    wherein the first and other DNA segments are connected in-frame; and    wherein the first and other DNA segments encode the fusion protein.    
     
     
         35 . A DNA construct encoding a fusion protein, the DNA construct comprising: 
 a first DNA segment encoding a zcytor17 soluble receptor wherein the zcytor17 soluble receptor comprises an amino acid sequence of 33-532 of SEQ ID NO:54;    at least one other DNA segment encoding an additional polypeptide;    wherein the first and other DNA segments are connected in-frame; and    wherein the first and other DNA segments encode the fusion protein.    
     
     
         36 . The DNA construct of  claim 35  wherein the at least one other DNA segment encodes a polypeptide comprising a human immunoglobulin Fc4.  
     
     
         37 . An expression vector comprising the following operably linked elements: 
 a transcription promoter;    a DNA construct encoding a fusion protein of  claim 35;  and    a transcription terminator,    wherein the promoter is operably linked to the DNA construct, and the DNA construct is operably linked to the transcription terminator.    
     
     
         38 . A cultured cell comprising an expression vector of  claim 37 , wherein the cell expresses the fusion protein encoded by the DNA construct.  
     
     
         39 . A method of producing a polypeptide comprising: 
 culturing a cell according to  claim 32;  and    isolating the polypeptide produced by the cell.    
     
     
         40 . A method of producing a zcytor17 soluble receptor comprising: 
 culturing a cell according to  claim 33;  and    isolating the zcytor17 soluble receptor produced by the cell.    
     
     
         41 . A method of producing a fusion protein comprising: 
 culturing a cell according to  claim 38;  and    isolating the fusion protein produced by the cell.    
     
     
         42 . A method of producing an antibody to a polypeptide comprising: 
 inoculating an animal with a polypeptide comprising an amino acid sequence of 33-532 of SEQ ID NO:54;    wherein the polypeptide elicits an immune response in the animal to produce the antibody; and    isolating the antibody from the animal.    
     
     
         43 . An antibody produced by the method of  claim 42 , which specifically binds to a polypeptide comprising an amino acid sequence of 33-532 of SEQ ID NO:54.  
     
     
         44 . The antibody of  claim 43  wherein the antibody is a monoclonal antibody.  
     
     
         45 . The antibody of  claim 44  wherein the monoclonal antibody is a neutralizing monoclonal antibody.