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 - 18 . (canceled) 
     
     
         19 . A method for treating a disease or condition associated with decreased expression of functional KPP, comprising administering to a patient in need of such treatment a composition comprising a polypeptide and a pharmaceutically acceptable excipient, wherein the polypeptide is selected from the group consisting of:
 (i) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-43,   (ii) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:22-23, SEQ ID NO:28, SEQ ID NO:30-32, SEQ ID NO:36-41 and SEQ ID NO:43,   (iii) a polypeptide comprising a naturally occurring amino acid sequence at least 91% identical to the amino acid sequence of SEQ ID NO:5,   (iv) a polypeptide comprising a naturally occurring amino acid sequence at least 93% identical to the amino acid sequence of SEQ ID NO:27,   (v) a polypeptide comprising a naturally occurring amino acid sequence at least 94% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:35 and SEQ ID NO:29,   (vi) a polypeptide comprising a naturally occurring amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:11, and SEQ ID NO:20,   (vii) a polypeptide comprising a naturally occurring amino acid sequence at least 96% identical to the amino acid sequence of SEQ ID NO:9 and SEQ ID NO:18,   (viii) a polypeptide comprising a naturally occurring amino acid sequence at least 97% identical to the amino acid sequence selected from the group consisting of SEQ ID NO:26, SEQ ID NO:33, and SEQ ID NO:34,   (ix) a polypeptide comprising a naturally occurring amino acid sequence at least 98% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:6-7,   (x) a polypeptide comprising a naturally occurring amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:16,   (xi) a polypeptide consisting essentially of a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2-3, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12-15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:42,   (xii) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-43, and   (xiii) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-43.   
     
     
         20 - 29 . (canceled) 
     
     
         30 . A method for a diagnostic test for a condition or disease associated with the expression of KPP in a biological sample, the method comprising:
 a) combining the biological sample with an antibody under conditions suitable for the antibody to bind the polypeptide and form an antibody:polypeptide complex, and   b) detecting the complex, wherein the presence of the complex correlates with the presence of the polypeptide in the biological sample, and   wherein said antibody specifically binds to a polypeptide selected from the group consisting of:
 (i) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:1-43, 
 (ii) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:22-23, SEQ ID NO:28, SEQ ID NO:30-32, SEQ ID NO:36-41 and SEQ ID NO:43, 
 (iii) a polypeptide comprising a naturally occurring amino acid sequence at least 91% identical to the amino acid sequence of SEQ ID NO:5, 
 (iv) a polypeptide comprising a naturally occurring amino acid sequence at least 93% identical to the amino acid sequence of SEQ ID NO:27, 
 (v) a polypeptide comprising a naturally occurring amino acid sequence at least 94% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:35 and SEQ ID NO:29, 
 (vi) a polypeptide comprising a naturally occurring amino acid sequence at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:11 and SEQ ID NO:20, 
 (vii) a polypeptide comprising a naturally occurring amino acid sequence at least 96% identical to the amino acid sequence of SEQ ID NO:9 and SEQ ID NO:18, 
 (viii) a polypeptide comprising a naturally occurring amino acid sequence at least 97% identical to the amino acid sequence selected from the group consisting of SEQ ID NO:26, SEQ ID NO:33, and SEQ ID NO:34, 
 (ix) a polypeptide comprising a naturally occurring amino acid sequence at least 98% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:6-7, 
 (x) a polypeptide comprising a naturally occurring amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:16, 
 (xi) a polypeptide consisting essentially of a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2-3, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12-15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, and SEQ ID NO:42, 
 (xii) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-43, and 
 (xiii) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-43. 
   
     
     
         31 - 141 . (canceled) 
     
     
         142 . The method of  claim 30 , wherein the antibody specifically binds to a polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 13. 
     
     
         143 . The method of  claim 30 , wherein the antibody specifically binds to a polypeptide comprising the amino acid sequence of SEQ ID NO: 13. 
     
     
         144 . The method of  claim 30 , wherein the antibody specifically binds to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 13. 
     
     
         145 . The method of  claim 30 , wherein the antibody is:
 (a) a chimeric antibody;   (b) a single chain antibody;   (c) a Fab fragment;   (d) a F(ab′) 2  fragment; or   (e) a Fv fragment.   
     
     
         146 . The method of  claim 30 , wherein the antibody is a polyclonal antibody. 
     
     
         147 . The method of  claim 30 , wherein the antibody is a monoclonal antibody. 
     
     
         148 . The method of  claim 30 , wherein the antibody is produced by screening an immunoglobulin library. 
     
     
         149 . The method of  claim 30 , wherein the antibody is monoclonal and is produced using a technique selected from the group consisting of hybridoma technique, human B-cell hybridoma technique, and EBV-hybridoma technique. 
     
     
         150 . The method of  claim 19 , wherein the polypeptide comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 13. 
     
     
         151 . The method of  claim 19 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 13. 
     
     
         152 . The method of  claim 19 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 13. 
     
     
         153 . The method of  claim 19 , wherein the polypeptide comprise a heterologous polypeptide. 
     
     
         154 . The method of  claim 19 , wherein the polypeptide is a fusion protein. 
     
     
         155 . The method of  claim 19 , wherein the polypeptide is conjugated to a carrier protein or an aptamer. 
     
     
         156 . The method of  claim 19 , wherein the disease or condition associated with decreased expression of functional KPP is selected from the group consisting of cardiovascular diseases, immune system disorders, neurological disorders, disorders affecting growth and development, lipid disorders, cell proliferative disorders, and cancers.