Methods for using 22045, a human cyclic nucleotide phosphodiesterase

Abstract

The present invention relates to methods for using a human cyclic nucleotide phosphodiesterase belonging to the superfamily of mammalian phosphodiesterases. The invention also relates to methods for using polynucleotides encoding the phosphodiesterase. The invention relates to methods using the phosphodiesterase polypeptides and polynucleotides as a target for diagnosis and treatment in phosphodiesterase-mediated or -related disorders. The invention further relates to drug-screening methods using the phosphodiesterase polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the phosphodiesterase polypeptides and polynucleotides. The invention further relates to agonists and antagonists identifiefd by drug screening methods with the phosphodiesterase polypeptides and polynucleotides as a target.

That which is claimed:  
     
         1 . A method of identifying an inhibitor of a human cyclic phosphodiesterase protein comprising: 
 a) combining an agent to be tested with a host cell expressing human cyclic phosphodiesterase protein having an amino acid sequence as set forth in SEQ ID NO:1 under conditions suitable for detecting a phosphodiesterase activity; and    b) assessing the ability of the agent to inhibit the phosphodiesterase activity, whereby inhibition of the phosphodiesterase activity by the agent is indicative that the agent is an inhibitor;    wherein the host cell is selected from the group consisting of breast carcinoma cells and colon carcinoma cells.    
     
     
         2 . The method of  claim 1 , wherein the phosphodiesterase activity is a signaling activity or a cellular response.  
     
     
         3 . The method of  claim 1 , wherein detecting of a phosphodiesterase activity comprises measuring substrate consumption or measuring the production of end product or intermediates.  
     
     
         4 . The method of  claim 1 , wherein the agent is selected from the group consisting of a small molecule, a peptide, an antibody and an antibody fragment.  
     
     
         5 . An inhibitor of a human cyclic phosphodiesterase protein identified according to the method of  claim 1 , wherein the inhibitor is an antagonist.  
     
     
         6 . The method of  claim 1 , wherein the human cyclic phosphodiesterase protein is encoded by the nucleotide sequence set forth in SEQ ID NO:2.  
     
     
         7 . A method of identifying an inhibitor of a human cyclic phosphodiesterase protein comprising: 
 a) combining an agent to be tested with a host cell expressing a fusion protein, wherein one or more domains or subregions of the fusion protein comprise(s) the amino acid sequence set forth in SEQ ID NO:1, under conditions suitable for detecting a phosphodiesterase activity; and    b) assessing the ability of the agent to inhibit the phosphodiesterase activity, whereby inhibition of the phosphodiesterase activity by the agent is indicative that the agent is an inhibitor;    wherein the host cell is selected from the group consisting of breast carcinoma cells and colon carcinoma cells.    
     
     
         8 . The method of  claim 7 , wherein the phosphodiesterase activity is a signaling activity or a cellular response.  
     
     
         9 . The method of  claim 7 , wherein detecting of a phosphodiesterase activity comprises measuring substrate consumption or measuring the production of end product or intermediates.  
     
     
         10 . The method of  claim 7 , wherein the agent is selected from the group consisting of a small molecule, a peptide, an antibody and an antibody fragment.  
     
     
         11 . An inhibitor of a human cyclic phosphodiesterase protein identified according to the method of  claim 7 , wherein the inhibitor is an antagonist.  
     
     
         12 . The method of  claim 7 , wherein the one or more domains or subregions of the fusion protein comprising the amino acid sequence set forth in SEQ ID NO:1, is/are encoded by the nucleotide sequence set forth in SEQ ID NO:2.