Methods of antagonizing morphogens

Abstract

Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptors particularly OP-1-binding cell surface receptors; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAs; (4) methods and compositions for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods and compositions for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.

1 - 25 . (canceled)  
     
     
         26 . A method for antagonizing BMP-4 binding to a cell surface receptor, the method comprising the step of: 
 providing a cell expressing a said cell-surface receptor with a protein having binding specificity for a ligand binding domain of the cell-surface receptor, said ligand binding domain defined by:    (i) residues 24-152 of SEQ ID NO: 6 (ALK-3);    (ii) residues 23-122 of SEQ ID NO: 8 (ALK-6); or    (iii) a nucleotide sequence of a first nucleic acid capable of hybridizing under stringent conditions with a second nucleic acid comprising a sequence defined by nucleotides 256-552 of SEQ ID NO:7 (ALK-6), the stringent conditions being hybridization in 40% formamide, 5×SSPE, 5× Denhardt's Solution, 0.1% SDS at 37° C. overnight, then washing in 0.1×SSPE, 0.1% SDS at 50° C.;    said protein sharing at least 60% amino acid sequence identity or at least 70% homology with residues 335-431 of the sequence defined by SEQ ID NO: 10 (OP-1),    such that said protein, when provided to said cell, is competent to interact specifically with said receptor, thereby substantially inhibiting BMP-4 binding to said receptor.    
     
     
         27 . (canceled)  
     
     
         28 . The method of  claim 26 , wherein said protein is substantially incapable of inducing a morphogen-mediated response.  
     
     
         29 . The method of  claim 28 , wherein said morphogen mediated response is an OP-1 mediated response.  
     
     
         30 . The method of  claim 26 , wherein the cell further expresses Daf-4.