Human beta-adrenergic receptor kinase polypeptide and methods

Abstract

Various embodiments of the invention provide human kinases and phosphatases (KPP) polypeptides and polynucleotides which identify and encode KPP. Embodiments of the invention also provide expression vectors, host cells, antibodies, agonists, and antagonists. Other embodiments provide methods for diagnosing, treating, or preventing disorders associated with aberrant expression of KPP.

1 - 19 . (canceled) 
     
     
         20 . A method of screening a compound for effectiveness as an agonist of a polypeptide, the method comprising:
 a) contacting a sample comprising the polypeptide with a compound, and   b) detecting agonist activity in the sample,   wherein the polypeptide is selected from the group consisting of:
 (i) a polypeptide comprising an amino acid sequence of SEQ ID NO:13; 
 (ii) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO:13; 
 (iii) a polypeptide comprising a naturally occurring amino acid sequence at least 91% identical to the amino acid sequence of SEQ ID NO:13; 
 (iv) a polypeptide comprising a naturally occurring amino acid sequence at least 93% identical to the amino acid sequence of SEQ ID NO:13, 
 (v) a polypeptide comprising a naturally occurring amino acid sequence at least 94% identical to an amino acid sequence of SEQ ID NO:13; 
 (vi) a polypeptide comprising a naturally occurring amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO:13; 
 (vii) a polypeptide comprising a naturally occurring amino acid sequence at least 96% identical to the amino acid sequence of SEQ ID NO:13; 
 (viii) a polypeptide comprising a naturally occurring amino acid sequence at least 97% identical to the amino acid sequence of SEQ ID NO:13; 
 (ix) a polypeptide comprising a naturally occurring amino acid sequence at least 98% identical to an amino acid sequence of SEQ ID NO:13; 
 (x) a polypeptide comprising a naturally occurring amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:13; 
 (xi) a polypeptide consisting essentially of a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO:13; 
 (xii) a biologically active fragment of a polypeptide having an amino acid sequence of SEQ ID NO:13; and 
 (xiii) an immunogenic fragment of a polypeptide having an amino acid sequence of SEQ ID NO:13. 
   
     
     
         21 .- 22 . (canceled) 
     
     
         23 . A method of screening a compound for effectiveness as an antagonist of a polypeptide, the method comprising:
 (a) contacting a sample comprising the polypeptide with a compound, and   (b) detecting antagonist activity in the sample,   wherein the polypeptide is selected from the group consisting of:
 (i) a polypeptide comprising an amino acid sequence of SEQ ID NO:13; 
 (ii) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO:13; 
 (iii) a polypeptide comprising a naturally occurring amino acid sequence at least 91% identical to the amino acid sequence of SEQ ID NO:13; 
 (iv) a polypeptide comprising a naturally occurring amino acid sequence at least 93% identical to the amino acid sequence of SEQ ID NO:13, 
 (v) a polypeptide comprising a naturally occurring amino acid sequence at least 94% identical to an amino acid sequence of SEQ ID NO:13; 
 (vi) a polypeptide comprising a naturally occurring amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO:13; 
 (vii) a polypeptide comprising a naturally occurring amino acid sequence at least 96% identical to the amino acid sequence of SEQ ID NO:13; 
 (viii) a polypeptide comprising a naturally occurring amino acid sequence at least 97% identical to the amino acid sequence of SEQ ID NO:13; 
 (ix) a polypeptide comprising a naturally occurring amino acid sequence at least 98% identical to an amino acid sequence of SEQ ID NO:13; 
 (x) a polypeptide comprising a naturally occurring amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:13; 
 (xi) a polypeptide consisting essentially of a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO:13; 
 (xii) a biologically active fragment of a polypeptide having an amino acid sequence of SEQ ID NO:13; and 
 (xiii) an immunogenic fragment of a polypeptide having an amino acid sequence of SEQ ID NO:13. 
   
     
     
         24 .- 25 . (canceled) 
     
     
         26 . A method of screening for a compound that specifically binds to a polypeptide, the method comprising:
 (a) combining the polypeptide with at least one test compound under suitable conditions, and   (b) detecting binding of the polypeptide to the test compound, thereby identifying a compound that specifically binds to the polypeptide,   
       wherein the polypeptide is selected from the group consisting of:
 (i) a polypeptide comprising an amino acid sequence of SEQ ID NO:13; 
 (ii) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO:13; 
 (iii) a polypeptide comprising a naturally occurring amino acid sequence at least 91% identical to the amino acid sequence of SEQ ID NO:13; 
 (iv) a polypeptide comprising a naturally occurring amino acid sequence at least 93% identical to the amino acid sequence of SEQ ID NO:13, 
 (v) a polypeptide comprising a naturally occurring amino acid sequence at least 94% identical to an amino acid sequence of SEQ ID NO:13; 
 (vi) a polypeptide comprising a naturally occurring amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO:13; 
 (vii) a polypeptide comprising a naturally occurring amino acid sequence at least 96% identical to the amino acid sequence of SEQ ID NO:13; 
 (viii) a polypeptide comprising a naturally occurring amino acid sequence at least 97% identical to the amino acid sequence of SEQ ID NO:13; 
 (ix) a polypeptide comprising a naturally occurring amino acid sequence at least 98% identical to an amino acid sequence of SEQ ID NO:13; 
 (x) a polypeptide comprising a naturally occurring amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:13; 
 (xi) a polypeptide consisting essentially of a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO:13; 
 (xii) a biologically active fragment of a polypeptide having an amino acid sequence of SEQ ID NO:13; and 
 (xiii) an immunogenic fragment of a polypeptide having an amino acid sequence of SEQ ID NO:13. 
 
     
     
         27 . A method of screening for a compound that modulates the activity of a polypeptide, the method comprising:
 (a) combining the polypeptide with at least one test compound under conditions permissive for the activity of the polypeptide,   (b) assessing the activity of the polypeptide in the presence of the test compound, and   (c) comparing the activity of the polypeptide in the presence of the test compound with the activity of the polypeptide in the absence of the test compound, wherein a change in the activity of the polypeptide in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide,   wherein the polypeptide is selected from the group consisting of:
 (i) a polypeptide comprising an amino acid sequence of SEQ ID NO:13; 
 (ii) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO:13; 
 (iii) a polypeptide comprising a naturally occurring amino acid sequence at least 91% identical to the amino acid sequence of SEQ ID NO:13; 
 (iv) a polypeptide comprising a naturally occurring amino acid sequence at least 93% identical to the amino acid sequence of SEQ ID NO:13, 
 (v) a polypeptide comprising a naturally occurring amino acid sequence at least 94% identical to an amino acid sequence of SEQ ID NO:13; 
 (vi) a polypeptide comprising a naturally occurring amino acid sequence at least 95% identical to an amino acid sequence of SEQ ID NO:13; 
 (vii) a polypeptide comprising a naturally occurring amino acid sequence at least 96% identical to the amino acid sequence of SEQ ID NO:13; 
 (viii) a polypeptide comprising a naturally occurring amino acid sequence at least 97% identical to the amino acid sequence of SEQ ID NO:13; 
 (ix) a polypeptide comprising a naturally occurring amino acid sequence at least 98% identical to an amino acid sequence of SEQ ID NO:13; 
 (x) a polypeptide comprising a naturally occurring amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:13; 
 (xi) a polypeptide consisting essentially of a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence of SEQ ID NO:13; 
 (xii) a biologically active fragment of a polypeptide having an amino acid sequence of SEQ ID NO:13; and 
 (xiii) an immunogenic fragment of a polypeptide having an amino acid sequence of SEQ ID NO:13. 
   
     
     
         28 - 141 . (canceled) 
     
     
         142 . The method of  claim 20 , wherein the polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 13. 
     
     
         143 . The method of  claim 20 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         144 . The method of  claim 20 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 13. 
     
     
         144 . The method of  claim 20 , wherein the compound is an antibody. 
     
     
         145 . The method of  claim 23 , wherein the polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 13. 
     
     
         146 . The method of  claim 23 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         147 . The method of  claim 23 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 13. 
     
     
         148 . The method of  claim 23 , wherein the compound is an antibody. 
     
     
         149 . The method of  claim 26 , wherein the polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 13. 
     
     
         150 . The method of  claim 26 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         151 . The method of  claim 26 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 13. 
     
     
         152 . The method of  claim 26 , wherein the compound is an antibody. 
     
     
         153 . The method of  claim 27 , wherein the polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 13. 
     
     
         154 . The method of  claim 27 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         155 . The method of  claim 27 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 13. 
     
     
         156 . The method of  claim 27 , wherein the compound is an antibody.