Proteins having serine/threonine kinase domains, corresponding nucleic acid molecules, and their use

Abstract

The invention relates to the molecule referred to as ALK-1, and its role as a type I receptor for members of the TGF-β family. The molecule has a role in the phosphorylation of Smad-5 and Smad1, which also act as activators of certain genes. Aspects of the invention relate to this interaction.

1 - 28 . (cancelled)  
     
     
         29  A method for determining if a substance inhibits binding of TGF-β to Alk-1 comprising contacting a cell that expresses an Alk-1 with said substance in the presence of TGF-β and determining if said substance inhibits binding of TGF-β to Alk-1.  
     
     
         30  The method of  claim 29 , wherein said substance is an antibody that binds to TGF-β.  
     
     
         31  The method of  claim 29 , wherein said substance is an antibody that binds to the extracellular domain of Alk-1.  
     
     
         32  The method of  claim 29  wherein said cells that express Alk-1 are transfected with a nucleic acid molecule which encodes Alk-1.  
     
     
         33  The method of  claim 29  wherein said Alk-1 is a constitutively active Alk-1.  
     
     
         34  The method of  claim 29 , wherein said Alk-1 is a kinase inactive Alk-1.  
     
     
         35  The method of  claim 32 , wherein said Alk-1 is an Alk-1 fusion polypeptide.  
     
     
         36  The method of  claim 35 , wherein said Alk-1 is fused to hemagglutinin.  
     
     
         37  The method of  claim 29 , wherein said cells that express Alk-1 are transfected with a nucleic acid molecule which encodes a Smad1 or a nucleic acid molecule which encodes a Smad5.  
     
     
         38  The method of  claim 37 , wherein said Smad1 is a Smad1 fusion polypeptide.  
     
     
         39  The method of  claim 38 , wherein said Smad1 is fused to Flag.  
     
     
         40  The method of  claim 37 , wherein said Smad5 is a Smad5 fusion polypeptide.  
     
     
         41  The method of  claim 40 , wherein said Smad5 is fused to Flag.  
     
     
         42  The method of  claim 29 , wherein inhibition of Smad1 or Smad5 phosphorylation in said cells that express an Alk-1 indicates inhibition of binding of TGF-β to Alk-1.