Novel type-1 cytokine receptor glm-r

Abstract

The present invention is directed to novel polypeptides and variants thereof of GLM-R polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Also provided are methods for detecting agents that modulate the activity of GLM-R. Also provided are methods for diagnosing and for treating disorders characterized by the over or under abundance of monocytes or macrophages.

1 . An isolated nucleic acid molecule which comprises DNA having at least about 80% sequence identity to (a) a DNA molecule encoding a GLM-R polypeptide comprising the sequence of amino acid residues from about 1 or about 20 to about 732 of  FIG. 2  (SEQ ID NO:2), or (b) the complement of the DNA molecule of (a).  
     
     
         2 . The isolated nucleic acid molecule of  claim 1  comprising the sequence of nucleotide positions from about 63 or about 120 to about 2258 of  FIG. 1  (SEQ ID NO:1).  
     
     
         3 . The isolated nucleic acid molecule of  claim 1  comprising the nucleotide sequence of  FIG. 1  (SEQ ID NO:1).  
     
     
         4 . The isolated nucleic acid molecule of  claim 1  comprising a nucleotide sequence that encodes the sequence of amino acid residues from about 1 or about 20 to about 732 of  FIG. 2  (SEQ ID NO:2).  
     
     
         5 . An isolated nucleic acid molecule comprising DNA which comprises at least about 80% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA deposited with the ATCC on May 16, 2000 under ATCC Deposit No. 1874-PTA (DNA173920-2924), or (b) the complement of the DNA molecule of (a).  
     
     
         6 . The isolated nucleic acid molecule of  claim 5  comprising DNA encoding the same mature polypeptide encoded by the human protein cDNA deposited with the ATCC on May 16, 2000 under ATCC Deposit No. 1874-PTA (DNA173920-2924).  
     
     
         7 . An isolated nucleic acid molecule comprising DNA which comprises at least about 80% sequence identity to (a) the full-length polypeptide coding sequence of the human protein cDNA deposited with the ATCC on May 16, 2000 under ATCC Deposit No. 1874-PTA (DNA173920-2924), or (b) the complement of the coding sequence of (a).  
     
     
         8 . The isolated nucleic acid molecule of  claim 7  comprising the full-length polypeptide coding sequence of the human protein cDNA deposited with the ATCC on May 16, 2000 under ATCC Deposit No. 1874-PTA (DNA173920-2924).  
     
     
         9 . An isolated nucleic acid molecule encoding a GLM-R polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence that encodes amino acids 1 or about 20 to about 732 of  FIG. 2  (SEQ ID NO:2).  
     
     
         10 . The isolated nucleic acid molecule of  claim 9 , wherein the nucleic acid that encodes amino acids 1 or about 20 to about 732 of  FIG. 2  (SEQ ID NO:2) comprises nucleotides 63 or about 120 to about 2258 of  FIG. 1  (SEQ ID NO:1).  
     
     
         11 . The isolated nucleic acid molecule of  claim 9 , wherein the hybridization occurs under stringent hybridization and wash conditions.  
     
     
         12 . An isolated nucleic acid molecule comprising at least about 702 nucleotides and which is produced by hybridizing a test DNA molecule under stringent hybridization conditions with (a) a DNA molecule which encodes a GLM-R polypeptide comprising a sequence of amino acid residues from 1 or about 20 to about 732 of  FIG. 2  (SEQ ID NO:2), or (b) the complement of the DNA molecule of (a), and isolating the test DNA molecule.  
     
     
         13 . The isolated nucleic acid molecule of  claim 12 , which has at least about 80% sequence identity to (a) or (b).  
     
     
         14 . A vector comprising the nucleic acid molecule of any one of  claims 1  to  13 .  
     
     
         15 . The vector of  claim 14 , wherein said nucleic acid molecule is operably linked to control sequences recognized by a host cell transformed with the vector.  
     
     
         16 . A nucleic acid molecule deposited with the ATCC under accession number 1874-PTA (DNA173920-2924).  
     
     
         17 . A host cell comprising the vector of  claim 16 .  
     
     
         18 . The host cell of  claim 17 , wherein said cell is a CHO cell.  
     
     
         19 . The host cell of  claim 17 , wherein said cell is an  E. coli.    
     
     
         20 . The host cell of  claim 17 , wherein said cell is a yeast cell.  
     
     
         21 . A process for producing a GLM-R polypeptide comprising culturing the host cell of  claim 17  under conditions suitable for expression of said GLM-R polypeptide and recovering said GLM-R polypeptide from the cell culture.  
     
     
         22 . An isolated GLM-R polypeptide comprising an amino acid sequence comprising at least about 80% sequence identity to the sequence of amino acid residues from about 1 or about 20 to about 732 of  FIG. 2  (SEQ ID NO:2).  
     
     
         23 . The isolated GLM-R polypeptide of  claim 22  comprising amino acid residues 1 or about 20 to about 732 of  FIG. 2  (SEQ ID NO:2).  
     
     
         24 . An isolated GLM-R polypeptide having at least about 80% sequence identity to the polypeptide encoded by the cDNA insert of the vector deposited with the ATCC on May 16, 2000 as ATCC Deposit No. 1874-PTA (DNA173920-2924).  
     
     
         25 . The isolated GLM-R polypeptide of  claim 24  which is encoded by the cDNA insert of the vector deposited with the ATCC on May 16, 2000 as ATCC Deposit No. 1874-PTA (DNA173920-2924).  
     
     
         26 . An isolated GLM-R polypeptide comprising the sequence of amino acid residues from 1 or about 20 to about 732 of  FIG. 2  (SEQ ID NO:2), or a fragment thereof sufficient to provide a binding site for an anti-GLM-R antibody.  
     
     
         27 . An isolated polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a GLM-R polypeptide comprising the sequence of amino acid residues from 1 or about 20 to about 732 of  FIG. 2  (SEQ ID NO:2), or (b) the complement of the DNA molecule of (a), (ii) culturing a host cell comprising said test DNA molecule under conditions suitable for the expression of said polypeptide, and (iii) recovering said polypeptide from the cell culture.  
     
     
         28 . The isolated polypeptide of  claim 27 , wherein said test DNA has at least about 80% sequence identity to (a) or (b).  
     
     
         29 . A chimeric molecule comprising a GLM-R polypeptide fused to a heterologous amino acid sequence.  
     
     
         30 . The chimeric molecule of  claim 29 , wherein said heterologous amino acid sequence is an epitope tag sequence.  
     
     
         31 . The chimeric molecule of  claim 29 , wherein said heterologous amino acid sequence is a Fc region of an immunoglobulin.  
     
     
         32 . An antibody which specifically binds to a GLM-R polypeptide.  
     
     
         33 . The antibody of  claim 32 , wherein said antibody is a monoclonal antibody.  
     
     
         34 . The antibody of  claim 32 , wherein said antibody is a humanized antibody.  
     
     
         35 . The antibody of  claim 32 , wherein said antibody is an antibody fragment.  
     
     
         36 . An agonist to a GLM-R polypeptide.  
     
     
         37 . An antagonist to a GLM-R polypeptide.  
     
     
         38 . A composition of matter comprising (a) a GLM-R polypeptide, (b) an agonist to a GLM-R polypeptide, (c) an antagonist to a GLM-R polypeptide, or (d) an anti-GLM-R antibody in admixture with a pharmaceutically acceptable carrier.  
     
     
         39 . An isolated nucleic acid molecule which comprises a nucleotide sequence having at least about 80% sequence identity to (a) a DNA molecule encoding amino acids 1 to X of  FIG. 2  (SEQ ID NO:2), where X is any amino acid from 510 to 519 of  FIG. 2  (SEQ ID NO:2), or (b) the complement of the DNA molecule of (a).  
     
     
         40 . The isolated nucleic acid of  claim 39  which comprises (a) a nucleotide sequence encoding amino acids 1 to X of  FIG. 2  (SEQ ID NO:2), where X is any amino acid from 510 to 519 of  FIG. 2  (SEQ ID NO:2), or (b) the complement of the nucleotide sequence of (a).  
     
     
         41 . An isolated soluble GLM-R polypeptide comprising an amino acid sequence having at least about 80% sequence identity to amino acids 1 to X of  FIG. 2  (SEQ ID NO:2), where X is any amino acid from 510 to 519 of  FIG. 2  (SEQ ID NO:2).  
     
     
         42 . The isolated soluble GLM-R polypeptide of  claim 41  which comprises amino acids 1 to X of  FIG. 2  (SEQ ID NO:2), where X is any amino acid from 510 to 519 of  FIG. 2  (SEQ ID NO:2).  
     
     
         43 . A method for screening for a bioactive agent capable of binding to GLM-R comprising: 
 a) adding a candidate bioactive agent to a sample of GLM-R; and    b) determining the binding of said candidate agent to said GLM-R, wherein binding indicates a bioactive agent capable of binding to GLM-R.    
     
     
         44 . A method for screening for a bioactive agent capable of modulating the activity of GLM-R, said method comprising the steps of: 
 a) adding a candidate bioactive agent to a sample of GLM-R; and    b) determining an alteration in the biological activity of GLM-R, wherein an alteration indicates a bioactive agent capable of modulating the activity of GLM-R.    
     
     
         45 . A method of identifying a receptor for GLM-R, said method comprising combining GLM-R with a composition comprising cell membrane material wherein said GLM-R complexes with a receptor on said cell membrane material, and identifying said receptor as a GLM-R receptor.  
     
     
         46 . The method of  claim 44  wherein GLM-R binds to said receptor, and said method further includes a step of crosslinking said GLM-R and receptor.  
     
     
         47 . The method of  claim 44 , wherein said composition is a cell.  
     
     
         48 . The method of  claim 44 , wherein said composition is a cell membrane extract preparation.  
     
     
         49 . A rodent comprising a genome comprising a transgene encoding GLM-R.