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 . (canceled) 
     
     
         29 . An isolated antibody that binds to the protein encoded by the nucleic acid molecule of SEQ ID NO: 1 and inhibits the phosphorylation of Smad-1. 
     
     
         30 . The isolated antibody of  claim 29 , wherein the antibody binds to the extracellular domain of the protein encoded by the nucleic acid molecule of SEQ ID NO: 1. 
     
     
         31 . The isolated antibody of  claim 29 , wherein the antibody inhibits the binding of TGF-β with ALK-1. 
     
     
         32 . The isolated antibody of  claim 29 , wherein the antibody binds to the extracellular domain of the protein of SEQ ID NO: 2. 
     
     
         33 . The isolated antibody of  claim 30 , wherein the antibody is a monoclonal antibody. 
     
     
         34 . A method for determining that an antibody which binds to the extracellular domain of Alk-1 inhibits Smad-1 phosphorylation, the method comprising contacting a cell that expresses Alk-1 with said antibody and determining if said antibody inhibits phosphorylation of Smad-1. 
     
     
         35 . The method of  claim 34 , wherein antibody binds to the extracellular domain of SEQ ID NO: 2. 
     
     
         36 . The method of  claim 34 , wherein said cell is an endothelial cell. 
     
     
         37 . The method of  claim 34 , wherein said cell that expresses Alk-1 is transfected with a nucleic acid molecule which encodes Alk-1. 
     
     
         38 . The method of  claim 34 , wherein said cell that expresses Alk-1 is transfected with a nucleic acid molecule which encodes a Smad-1. 
     
     
         39 . The method of  claim 34 , wherein the cell expresses human Alk-1. 
     
     
         40 . A method for determining that an antibody which binds to the extracellular domain of Alk-1 inhibits Smad-1 regulated gene expression, the method comprising contacting a cell that expresses Alk-1 with said antibody and determining if said antibody inhibits the expression of a gene that is activated by phosphorylated Smad-1. 
     
     
         41 . The method of  claim 40 , wherein antibody binds to the extracellular domain of SEQ ID NO: 2. 
     
     
         42 . The method of  claim 40 , wherein said cell is an endothelial cell. 
     
     
         43 . The method of  claim 40 , wherein said cell that expresses Alk-1 is transfected with a nucleic acid molecule which encodes Alk-1. 
     
     
         44 . The method of  claim 40 , wherein said cell that expresses Alk-1 is transfected with a nucleic acid molecule which encodes a Smad-1. 
     
     
         45 . The method of  claim 40 , wherein the cell expresses human Alk-1.