Insulin receptor tyrosine kinase substrate

Abstract

The invention provides a human insulin receptor tyrosine kinase substrate (IRS-p53h) and polynucleotides which identify and encode IRS-p53h. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for treating or preventing disorders associated with expression of IRS-p53h.

What is claimed is:  
     
         1 . An isolated antibody which specifically binds to a polypeptide comprising an amino acid sequence of SEQ ID NO:3.  
     
     
         2 . The antibody of  claim 1 , 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 humanized antibody.    
     
     
         3 . A composition comprising an antibody of  claim 1  and an acceptable excipient.  
     
     
         4 . A method of diagnosing a condition or disease associated with the expression of IRS-p53h-2 in a subject, comprising administering to said subject an effective amount of the composition of  claim 3 .  
     
     
         5 . A composition of  claim 3 , wherein the antibody is labeled.  
     
     
         6 . A method of diagnosing a condition or disease associated with the expression of IRS-p53h-2 in a subject, comprising administering to said subject an effective amount of the composition of  claim 5 .  
     
     
         7 . A method of preparing a polyclonal antibody with the specificity of the antibody of  claim 1 , the method comprising: 
 a) immunizing an animal with a polypeptide consisting of an amino acid sequence of SEQ ID NO:3, or an immunogenic fragment thereof, under conditions to elicit an antibody response,    b) isolating antibodies from said animal, and    c) screening the isolated antibodies with the polypeptide, thereby identifying a polyclonal antibody which binds specifically to a polypeptide comprising an amino acid sequence of SEQ ID NO:3.    
     
     
         8 . A polyclonal antibody produced by a method of  claim 7 .  
     
     
         9 . A composition comprising the polyclonal antibody of  claim 8  and a suitable carrier.  
     
     
         10 . A method of making a monoclonal antibody with the specificity of the antibody of  claim 1 , the method comprising: 
 a) immunizing an animal with a polypeptide consisting of an amino acid sequence of SEQ ID NO:3, or an immunogenic fragment thereof, under conditions to elicit an antibody response,    b) isolating antibody producing cells from the animal,    c) fusing the antibody producing cells with immortalized cells to form monoclonal antibody-producing hybridoma cells,    d) culturing the hybridoma cells, and    e) isolating from the culture monoclonal antibody which binds specifically to a polypeptide comprising an amino acid sequence of SEQ ID NO:3.    
     
     
         11 . A monoclonal antibody produced by a method of  claim 10 .  
     
     
         12 . A composition comprising the monoclonal antibody of  claim 11  and a suitable carrier.  
     
     
         13 . The antibody of  claim 1 , wherein the antibody is produced by screening a Fab expression library.  
     
     
         14 . The antibody of  claim 1 , wherein the antibody is produced by screening a recombinant immunoglobulin library.  
     
     
         15 . A method of detecting a polypeptide comprising an amino acid sequence of SEQ ID NO:3 in a sample, the method comprising: 
 a) incubating the antibody of  claim 11  with a sample under conditions to allow specific binding of the antibody and the polypeptide, and    b) detecting specific binding, wherein specific binding indicates the presence of a polypeptide comprising an amino acid sequence of SEQ ID NO:3 in the sample.    
     
     
         16 . A method of purifying a polypeptide comprising an amino acid sequence of SEQ ID NO:3 from a sample, the method comprising: 
 a) incubating the antibody of  claim 1  with a sample under conditions to allow specific binding of the antibody and the polypeptide, and    b) separating the antibody from the sample and obtaining the purified polypeptide comprising an amino acid sequence of SEQ ID NO:3.    
     
     
         17 . The method of  claim 5 , wherein the disease or condition is a disorder of the insulin response and is selected from the group consisting of type 2 (non-insulin-dependent) diabetes mellitus, hyperglycemia, myotonic muscular dystrophy, acanthosis nigricans, retinopathy, nephropathy, atherosclerotic coronary and peripheral arterial disease, and peripheral and autonomic neuropathies.  
     
     
         18 . The method of  claim 6  wherein the disease or condition is Alzheimer's disease.  
     
     
         19 . A method of treating or preventing a disease or condition associated with increased expression of IRS-p53h-2, the method comprising administering to a subject in need of such treatment the composition of  claim 9 .  
     
     
         20 . A method of treating or preventing a disease or condition associated with increasedd expression of IRS-p53h-2, the method comprising administering to a subject in need of such treatment the composition of  claim 12.