Methods for treatment or diagnosis of disease or disorders associated with an APB domain

Abstract

The present invention concerns methods for diagnosis and treatment of diseases or disorders characterized by abnormal cellular signal transduction involving a newly identified region, herein termed the “APB domain.” APB domain binding between proteins is believed to play an important role in signal transduction pathways and, thereby, influence cellular events. Thus, APB mediated activity plays a role in signal transduction pathways and agents modulating APB mediated activity can be used to treat diseases or disorders involving proteins containing APB domains.

1 - 12 . (Canceled)  
     
     
         13 . A method of assaying for agents useful for disrupting APB interactions or in the diagnosis of APB diseases or disorders, comprising the step of measuring the ability of an agent to bind to an APB recognition region or an APB domain.  
     
     
         14 . The method of  claim 13 , wherein said APB domain has an amino acid region with at least 30% sequence similarity to the Shc APB domain.  
     
     
         15 . The method of  claim 13 , wherein said APB domain has an amino acid region with at least 20% sequence identity to the Shc APB domain.  
     
     
         16 - 18 . (Canceled)  
     
     
         19 . The method of  claim 13 , wherein the ability of an agent to bind to an APB recognition region is measured.  
     
     
         20 . The method of  claim 13 , wherein the ability of an agent to bind to an APB domain is measured.  
     
     
         21 . The method of  claim 13 , wherein said agent is an antibody.  
     
     
         22 . The method of  claim 13 , wherein said agent is a polypeptide comprising at least 10 amino acids, including the amino acid sequence Asparagine-Proline-X-(phosphorylated) Tyrosine.  
     
     
         23 . A method of identifying an agent able to bind to an APB domain or an APB recognition region, comprising: 
 (a) exposing at least one agent to a protein comprising an APB domain or an APB recognition region for a time sufficient to allow binding of the agent;    (b) removing non-bound agents; and    (c) determining the presence of bound agent.    
     
     
         24 . The method of  claim 23 , wherein multiple agents are simultaneously screened.  
     
     
         25 . A method of identifying an agent able to promote APB binding complexes, comprising: 
 (a) exposing a first polypeptide containing an APB domain or APB recognition region to a candidate agent; and    (b) measuring the ability of a second polypeptide containing an APB domain or APB recognition region to form a complex with said first polypeptide containing an APB domain or APB recognition region.    
     
     
         26 . A method of identifying an agent able to promote APB binding complexes, comprising: 
 (a) exposing a cell capable of forming an APB binding complex to a candidate agent;    (b) lysing said cell;    (c) exposing the cell lysate to an antibody that binds to a component of an APB binding complex; and    (d) measuring APB complex formation.    
     
     
         27 . The method of  claim 26 , wherein step (d) employs immunoprecipitation.  
     
     
         28 . The method of  claim 26 , wherein said antibody is bound to a solid support.