G-protein parathyroid hormone receptor HLTDG74

Abstract

Human G-protein parathyroid hormone (PTH) receptor polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptides for identifying antagonists and agonists to such polypeptides and methods of using the agonists and antagonists therapeutically to treat conditions related to the underexpression and overexpression of the PTH receptor receptor polypeptides. Also disclosed are diagnostic methods for detecting a mutation in the PTH receptor receptor nucleic acid sequences and detecting a level of the soluble form of the receptors in a sample derived from a host.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding the polypeptide as set forth in FIG. 1.    (b) a polynucleotide encoding the polypeptide expressed by the DNA contained in ATCC Deposit No. ______;    (c) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a); and    (d) a polynucleotide fragment of the polynucleotide of (a) or (b).    
     
     
         2 . The polynucleotide of  claim 1  encoding the polypeptide as set forth in FIG. 1.  
     
     
         3 . The polynucleotide of  claim 1  wherein said polynucleotide encodes a mature polypeptide expressed by the DNA contained in ATCC Deposit No. ______.  
     
     
         4 . A vector containing the polynucleotide of  claim 1 .  
     
     
         5 . A host cell transformed or transfected with the vector of  claim 4 .  
     
     
         6 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 5  the polypeptide encoded by said polynucleotide.  
     
     
         7 . A process for producing cells capable of expressing a polypeptide comprising transforming or transfecting the cells with the vector of  claim 4 .  
     
     
         8 . A receptor polypeptide selected from the group consisting of: 
 (i) a polypeptide having the deduced amino acid sequence of FIG. 1 and fragments, analogs and derivatives thereof; and    (ii) a polypeptide encoded by the cDNA of ATCC Deposit No. ______ and fragments, analogs and derivatives of said polypeptide.    
     
     
         9 . The polypeptide of  claim 8  wherein the polypeptide has the deduced amino acid sequence of SEQ ID NO:2.  
     
     
         10 . An antibody against the polypeptide of  claim 8 .  
     
     
         11 . A compound which activates the polypeptide of  claim 8 .  
     
     
         12 . A compound which inhibits activation the polypeptide of  claim 8 .  
     
     
         13 . A method for the treatment of a patient having need to activate a PTH receptor receptor comprising: administering to the patient a therapeutically effective amount of the compound of  claim 11 .  
     
     
         14 . A method for the treatment of a patient having need to inhibit a PTH receptor receptor comprising: administering to the patient a therapeutically effective amount of the compound of  claim 12 .  
     
     
         15 . The method of  claim 13  wherein said compound is a polypeptide and a therapeutically effective amount of the compound is administered by providing to the patient DNA encoding said agonist and expressing said agonist in vivo.  
     
     
         16 . The method of  claim 14  wherein said compound is a polypeptide and a therapeutically effective amount of the compound is administered by providing to the patient DNA encoding said antagonist and expressing said antagonist in vivo.  
     
     
         17 . A method for identifying compounds which bind to and activate the receptor polypeptide of  claim 8  comprising: 
 contacting a cell expressing on the surface thereof the receptor polypeptide, said receptor being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said receptor polypeptide, with a compound under conditions sufficient to permit binding of the compound to the receptor polypeptide; and  
 identifying if the compound is capable of receptor binding by detecting the signal produced by said second component.  
 
     
     
         18 . A method for identifying compounds which bind to and inhibit activation of the polypeptide of  claim 8  comprising: 
 contacting a cell expressing on the surface thereof the receptor polypeptide of  claim 8 , said receptor being associated with a second component capable of providing a detectable signal in response to the binding of a compound to said receptor polypeptide, with an analytically detectable ligand known to bind to the receptor polypeptide and a compound to be screened under conditions to permit binding to the receptor polypeptide; and  
 determining whether the compound inhibits activation of the polypeptide by detecting the absence of a signal generated from the interaction of the ligand with the polypeptide.  
 
     
     
         19 . A process for diagnosing in a patient a disease or a susceptibility to a disease related to an under-expression of the polypeptide of  claim 8  comprising: 
 determining a mutation in the nucleic acid sequence encoding the polypeptide of  claim 8  in a sample derived from a patient.  
 
     
     
         20 . A diagnostic process comprising: 
 analyzing for the presence of the polypeptide of  claim 8  in a sample derived from a host.