Calcium-sensing receptor 2 (CaR2) and methods for using

Abstract

The current disclosure provide a novel human calcium sensing receptor named CaR2 and the nucleotide sequence that encodes the receptor. The disclosure further provides antibodies specific for CaR2. Also disclosed are methods of identifying modulators of the receptor and methods of using the identified modulators to treat calcium receptor mediated conditions.

What is claimed:  
     
         1 . An isolated nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2.  
     
     
         2 . A vector comprising the nucleic acid molecule of  claim 1 .  
     
     
         3 . The vector of  claim 2 , which is an expression vector.  
     
     
         4 . A host cell transfected with the vector of  claim 3 .  
     
     
         5 . An isolated polypeptide comprising the amino acid sequence set forth as SEQ ID NO:2.  
     
     
         6 . The polypeptide of anyone of  claim 5 , further comprising heterologous amino acid sequences.  
     
     
         7 . An antibody which selectively binds to the polypeptide  claim 5 , or a fragment thereof.  
     
     
         8 . A method for detecting the presence of a polypeptide in a sample, said method comprising contacting said sample with an agent that specifically allows detection of the presence of the polypeptide in the sample and then detecting the presence of the polypeptide, wherein said polypeptide is selected from the group consisting of: 
 (a) The amino acid sequence shown in SEQ ID NO: 2;    (b) The amino acid sequence of an allelic variant of the amino acid sequence shown in SEQ ID NO: 2;    (c) The amino acid sequence of a sequence variant of the amino acid sequence shown in SEQ ID NO: 2, wherein the sequence variant is encoded by a nucleic acid molecule hybridizing to the nucleic acid molecule shown in SEQ ID NO:1 under stringent conditions;    (d) A fragment of the amino acid sequence shown in SEQ ID NO: 2, wherein the fragment comprises at least 10 contiguous amino acids;    (e) The amino acid sequence of an epitope bearing region of anyone of the polypeptides of (a)-(e);    wherein said sample is derived from cells involved in abnormal cell proliferation.    
     
     
         9 . The method of  claim 8 , wherein said agent is capable of selective physical association with said polypeptide.  
     
     
         10 . The method of  claim 9 , wherein said agent binds to said polypeptide.  
     
     
         11 . The method of  claim 10 , wherein said agent is an antibody.  
     
     
         12 . A method for identifying an agent that modulates the level or activity of a nucleic acid molecule in a cell, wherein said nucleic acid molecule has a nucleic acid sequence selected from the group consisting of: 
 (a) The nucleotide sequence shown in SEQ ID NO:1;    (b) A nucleotide sequence encoding the amino acid sequence shown in SEQ ID NO: 2;    (c) A nucleotide sequence complementary to any of the nucleotide sequences in (a) or (b);    (d) A nucleotide sequence encoding an amino acid sequence of a sequence variant of the amino acid sequence shown in SEQ ID NO: 2 that hybridizes to the nucleotide sequence shown in SEQ ID NO:1 under stringent conditions;    (e) A nucleotide sequence encoding a fragment of the amino acid sequence shown in SEQ ID NO: 2, wherein the fragment comprises at least 10 contiguous amino acids;    said method comprising contacting said agent with a cell capable of expressing said nucleic acid molecule such that said nucleic acid molecule level or activity can be modulated in said cell by said agent and measuring said nucleic acid molecule level or activity.    
     
     
         13 . A method for identifying an agent that modulates the level or activity of a polypeptide in a cell, wherein said polypeptide is selected from the group consisting of: 
 (a) The amino acid sequence shown in SEQ ID NO:2;    (b) The amino acid sequence of an allelic variant of the amino acid sequence shown in SEQ ID NO: 2;    (c) The amino acid sequence of a sequence variant of the amino acid sequence shown in SEQ ID NO: 2, wherein the sequence variant is encoded by a nucleic acid molecule hybridizing to the nucleic acid molecule shown in SEQ ID NO:1 under stringent conditions;    (d) A fragment of the amino acid sequence shown in SEQ ID NO.2, wherein the fragment comprises at least 10 contiguous amino acids;    (e) The amino acid sequence of an epitope bearing region of anyone of the polypeptides of (a)-(d);    said method comprising: contacting said agent with a cell capable of expressing said polypeptide such that said polypeptide level or activity can be modulated in said cell by said agent and measuring said polypeptide level or activity.    
     
     
         14 . The method of  claim 13  wherein said agent decreases the level or activity of said polypeptide.  
     
     
         15 . A method of treating a subject with a calcium receptor mediated disorder comprising the step of administering a calcium receptor modulator identified by the method of  claim 12  to said individual such that the subject is treated.  
     
     
         16 . A method of treating a subject with a calcium receptor mediated disorder comprising the step of administering a calcium receptor modulator identified by the method of  claim 13  to said individual such that the subject is treated.  
     
     
         17 . A method of treating a subject with an osteocalcin mediated disorder comprising the step of administering a calcium receptor modulator identified by the method of  claim 12  to said individual such that the subject is treated.  
     
     
         18 . A method of treating a subject with an osteocalcin mediated disorder comprising the step of administering a calcium receptor modulator identified by the method of  claim 13  to said individual such that the subject is treated.  
     
     
         19 . The agent identified by the method of  claim 12 .  
     
     
         20 . The agent identified by the method of  claim 13.