Human prostate specific G-protein receptor HPRAJ70

Abstract

The present invention relates to PSGR, a novel prostate specific gene with homology to a G-protein coupled receptor overexpressed in prostate cancer. More specifically, the invention relates to PSGR polynucleotides and the polypeptides encoded by these polynucleotides, and the use of PSGR polynucleotides and polypeptides for detecting disorders of the reproductive system, including disorders of the prostate, particularly the presence of cancer. This invention relates to PSGR polynucleotides and polypeptides as well as vectors, host cells, antibodies directed to PSGR polynucleotides and polypeptides and recombinant and synthetic methods for producing the same. Also provided are methods for diagnosing, treating, preventing, and/or prognosing disorders related to the prostate, including cancer. The invention further relates to screening methods for identifying agonists and antagonists of PSGR polynucleotides and polypeptides of the invention and methods and/or compositions for inhibiting or enhancing the production and/or function of the PSGR polypeptides of the present invention.

1 . An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding a polypeptide comprising amino acids from about 1 to about 320 in SEQ ID NO:2;    (b) a nucleotide sequence encoding a polypeptide comprising amino acids from about 1 to about 320 in SEQ ID NO:4;    (c) a nucleotide sequence encoding a polypeptide comprising amino acids from about 2 to about 320 in SEQ ID NO:2;    (d) a nucleotide sequence encoding a polypeptide comprising amino acids from about 2 to about 320 in SEQ ID NO:4;    (e) a nucleotide sequence encoding PSGR having the amino acid sequence encoded by cDNA HPRAJ80 clone contained in ATCC Deposit No. 97131;    (f) a nucleotide sequence encoding any one of the PSGR extracellular domain;    (g) a nucleotide sequence encoding any one of the PSGR transmembrane domain;    (h) a nucleotide sequence encoding any one of the PSGR intracellular domain;    (i) a nucleotide sequence encoding any one of the PSGR extracellular and intracellular domains with all or part of the transmembrane domain deleted; and    (j) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), (g), (h), or (i).    
     
     
         2 . The nucleic acid molecule of  claim 1 , wherein said polynucleotide has the nucleotide sequence in SEQ ID NO:1.  
     
     
         3 . The nucleic acid molecule of  claim 1 , wherein said polynucleotide has the nucleotide sequence in SEQ ID NO:3.  
     
     
         4 . The nucleic acid molecule of  claim 1 , wherein said polynucleotide has the nucleotide sequence in SEQ ID NO:1 encoding the full length PSGR polypeptide having the amino acid sequence in SEQ ID NO:2.  
     
     
         5 . The nucleic acid molecule of  claim 1 , wherein said polynucleotide has the nucleotide sequence in SEQ ID NO:3 encoding the full length PSGR polypeptide having the amino acid sequence in SEQ ID NO:4.  
     
     
         6 . The nucleic acid molecule of  claim 1 , wherein said polynucleotide has the nucleotide sequence in SEQ ID NO:1 encoding a PSGR extracellular domain having the amino acid sequence in SEQ ID NO:2.  
     
     
         7 . The nucleic acid molecule of  claim 1 , wherein said polynucleotide has the complete nucleotide sequence of a cDNA clone contained in ATCC Deposit No. 97131.  
     
     
         8 . The nucleic acid molecule of  claim 1 , wherein said polynucleotide has the nucleotide sequence encoding the full length PSGR having the amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. 97131.  
     
     
         9 . The nucleic acid molecule of  claim 1 , wherein said polynucleotide has the nucleotide sequence encoding a PSGR extracellular domain having the amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. 97131.  
     
     
         10 . An isolated nucleic acid molecule comprising a polynucleotide which hybridizes under stringent hybridization conditions to a polynucleotide having a nucleotide sequence identical to a nucleotide sequence in (a), (b), (c), (d), (e), (f), (g), or (h) of  claim 1 , wherein said polynucleotide which hybridizes does not hybridize under stringent hybridization conditions to a polynucleotide having a nucleotide sequence consisting of only A residues or of only T residues.  
     
     
         11 . An isolated nucleic acid molecule comprising a polynucleotide which encodes the amino acid sequence of an epitope-bearing portion of PSGR having an amino acid sequence in (a), (b), (c), (d), (e), (f), (g), (h), or (i) of  claim 1 .  
     
     
         12 . The isolated nucleic acid molecule of  claim 9 , which encodes an epitope-bearing portion of PSGR selected from the group consisting of: 
 (a) a polypeptide comprising amino acid residues from about 50 to about 55 in SEQ ID NO:2;    (b) a polypeptide comprising amino acid residues from about 87 to about 90 in SEQ ID NO:2;    (c) a polypeptide comprising amino acid residues from about 227 to about 234 in SEQ ID NO:2; and    (d) a polypeptide comprising amino acid residues from about 309 to about 313 in SEQ ID NO:2.    
     
     
         13 . The isolated nucleic acid molecule of  claim 1 , which encodes any one of the PSGR extracellular domains.  
     
     
         14 . The isolated nucleic acid molecule of  claim 1 , which encodes any one of the PSGR transmembrane domains.  
     
     
         15 . The isolated nucleic acid molecule of  claim 1 , which encodes any one of the PSGR intracellular domains.  
     
     
         16 . A method for making a recombinant vector comprising inserting an isolated nucleic acid molecule of  claim 1  into a vector.  
     
     
         17 . A recombinant vector produced by the method of  claim 16 .  
     
     
         18 . A method of making a recombinant host cell comprising introducing the recombinant vector of  claim 16  into a host cell.  
     
     
         19 . A recombinant host cell produced by the method of  claim 18 .  
     
     
         20 . A recombinant method for producing a PSGR polypeptide, comprising culturing the recombinant host cell of  claim 19  under conditions such that said polypeptide is expressed, and recovering said polypeptide.  
     
     
         21 . An isolated PSGR polypeptide having an amino acid sequence at least 95% identical to a sequence selected from the group consisting of: 
 (a) amino acids from about 1 to about 320 in SEQ ID NO:2;    (b) amino acids from about 1 to about 320 in SEQ ID NO:4;    (c) amino acids from about 2 to about 320 in SEQ ID NO:2;    (d) amino acids from about 2 to about 320 in SEQ ID NO:4;    (e) the amino acid sequence of the full length PSGR polypeptide having the amino acid sequence encoded by cDNA HPRAJ80 clone contained in ATCC Deposit No. 97131;    (f) the amino acid sequence of any one of the PSGR extracellular domain;    (g) the amino acid sequence of any one of the PSGR transmembrane domain;    (h) the amino acid sequence of any one of the PSGR intracellular domain;    (i) the amino acid sequence of any one of the PSGR extracellular and intracellular domains with all or part of the transmembrane domain deleted; and    (j) the amino acid sequence of an epitope-bearing portion of any one of the polypeptides of (a), (b), (c), (d), (e), (f), (g), (h), and (i).    
     
     
         22 . An isolated polypeptide comprising an epitope-bearing portion of the PSGR protein, wherein said portion is selected from the group consisting of: 
 (a) a polypeptide comprising amino acid residues from about 50 to about 55 in SEQ ID NO:2;    (b) a polypeptide comprising amino acid residues from about 87 to about 90 in SEQ ID NO:2;    (c) a polypeptide comprising amino acid residues from about 227 to about 234 in SEQ ID NO:2; and    (d) a polypeptide comprising amino acid residues from about 309 to about 313 in SEQ ID NO:2.    
     
     
         23 . An isolated antibody that binds specifically to a PSGR polypeptide of  claim 21 .  
     
     
         24 . A method of treating diseases and disorders of the prostate comprising administering an effective amount of the polypeptide as claimed in  claim 21 , or an agonist thereof to a patient in need thereof.  
     
     
         25 . A method of treating diseases and disorders of the prostate comprising administering to a patient in need thereof an effective amount of an antagonist of the polypeptide as claimed in  claim 21  to a patient in need thereof.  
     
     
         26 . An isolated nucleic acid molecule comprising a polynucleotide encoding a PSGR polypeptide wherein, except for at least one conservative amino acid substitution, said polypeptide has a sequence selected from the group consisting of: 
 (a) a nucleotide sequence encoding a polypeptide comprising amino acids from about 1 to about 320 in SEQ ID NO:2;    (b) a nucleotide sequence encoding a polypeptide comprising amino acids from about 2 to about 320 in SEQ ID NO:2;    (c) a nucleotide sequence encoding PSGR having the amino acid sequence encoded by cDNA HPRAJ80 clone contained in ATCC Deposit No. 97131;    (d) a nucleotide sequence encoding any one of the PSGR extracellular domain;    (e) a nucleotide sequence encoding any one of the PSGR transmembrane domain;    (f) a nucleotide sequence encoding any one of the PSGR intracellular domain;    (g) a nucleotide sequence encoding any one of the PSGR extracellular and intracellular domains with all or part of the transmembrane domain deleted; and    (h) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), or (g).    
     
     
         27 . An isolated PSGR polypeptide wherein, except for at least one conservative amino acid substitution, said polypeptide has a sequence selected from the group consisting of: 
 (a) amino acids from about 1 to about 320 in SEQ ID NO:2;    (b) amino acids from about 2 to about 320 in SEQ ID NO:2;    (c) the amino acid sequence of the full length PSGR polypeptide having the amino acid sequence encoded by cDNA HPRAJ80 clone contained in ATCC Deposit No. 97131;    (d) the amino acid sequence of any one of the PSGR extracellular domain;    (e) the amino acid sequence of any one of the PSGR transmembrane domain;    (f) the amino acid sequence of any one of the PSGR intracellular domain;    (g) the amino acid sequence of any one of the PSGR extracellular and intracellular domains with all or part of the transmembrane domain deleted; and    (h) the amino acid sequence of an epitope-bearing portion of any one of the polypeptides of (a), (b), (c), (d), (e), (f), and (g).    
     
     
         28 . A vaccine comprising the polypeptide of  claim 21 , in combination with a pharmaceutical carrier.  
     
     
         29 . A pharmaceutical composition comprising: 
 (a) an antibody that specifically binds to a PSGR polypeptide, and    (b) a pharmaceutically acceptable carrier.