Novel cytokine designated elk ligand

Abstract

elk ligand (elk-L) polypeptides as well as DNA sequences, vectors and transformed host cells useful in providing elk-L polypeptides. The elk-L polypeptide binds to a cell surface receptor that is a member of the tyrosine kinase receptor family.

What is claimed is:  
     
         1 . An isolated DNA sequence encoding a biologically active human elk-L protein wherein said elk-L comprises an amino acid sequence selected from the group consisting of amino acids −24 to 322 of SEQ ID NO:2 and 1-322 of SEQ ID. NO:2.  
     
     
         2 . An isolated DNA sequence encoding a soluble human elk-L protein, wherein said elk-L comprises an amino acid sequence selected from the group consisting of amino acids −24 to 213 of SEQ ID NO:2 and 1-213 of SEQ ID NO:2.  
     
     
         3 . An isolated DNA capable of hybridizing to a DNA sequence of  claim 1  under moderately stringent conditions, wherein said isolated DNA encodes a biologically active elk-L protein.  
     
     
         4 . An expression vector comprising a DNA sequence according, to  claim 1 .  
     
     
         5 . An expression vector comprising a DNA sequence according, to  claim 2 .  
     
     
         6 . An expression vector comprising a DNA sequence according to  claim 3 .  
     
     
         7 . A process for preparing an elk-L polypeptide, comprising culturing a host cell transformed with a vector according to  claim 4  under conditions promoting expression of elk-L, and recovering the elk-L polypeptide from the culture.  
     
     
         8 . A process for preparing an elk-L polypeptide, comprising culturing a host cell transformed with a vector according to  claim 5  under conditions promoting expression of elk-L and recovering the elk-L polypeptide from the culture.  
     
     
         9 . A process for preparing an elk-L polypeptide, comprising culturing a host cell transformed with a vector according to  claim 6  under conditions promoting expression of elk-L, and recovering the elk-L polypeptide from the culture.  
     
     
         10 . A substantially homogeneous purified biologically active mature human elk-L protein characterized by the N-terminal amino acid sequence Ala-Thr-Pro-Leu-Ala-Lys-Asn-Leu-Glu-Pro-Val-Ser-.  
     
     
         11 . Purified elk-L according to  claim 10 , wherein said elk-L comprises an amino acid sequence selected from the group consisting of amino acids 1-322 of SEQ ID NO:2 and 1-213 of SEQ ID NO:2.  
     
     
         12 . Purified elk-L according to  claim 10 , wherein said elk-L comprises an amino acid sequence that is identical to amino acids 1-322 or 1-213 of SEQ ID NO:2, except for modification(s) selected from the group consisting of: 
 (a) inactivation of N-glycosylation site(s);    (b) inactivation of KEX2 protease processing site(s); and    (c) conservative amino acid substitution(s).    
     
     
         13 . Essentially homogeneous purified biologically active elk-L protein, wherein said elk-L is encoded by DNA that will hybridize to a DNA sequence of  claim 1  under moderately stringent conditions.  
     
     
         14 . An antibody immunoreactive with elk-L or an elk-L immunogen.  
     
     
         15 . An antibody according to  claim 14 , wherein said antibody is a monoclonal antibody.  
     
     
         16 . An antisense or sense oligonucleotide that can inhibit transcription or translation of elk-L, comprising a sequence of at least about 14 nucleotides corresponding to a DNA sequence according to  claim 1  or its DNA or RNA complement.  
     
     
         17 . A method for treating a mammal afflicted with an injury to or disorder of neural tissue, comprising administering to said mammal an effective amount of an elk-L protein of  claim 10 .  
     
     
         18 . A method of  claim 17 , wherein said elk-L protein is a soluble human elk-L protein.  
     
     
         19 . A method of  claim 17 , wherein said-injury or disorder is mediated or characterized at least in part by excitotoxicity.  
     
     
         20 . A soluble human elk-L/Fc fusion protein comprising amino acids 1-213 of SEQ ID NO:2 fused to the N-terminus of an Fc polypeptide.  
     
     
         21 . A dimer comprising two soluble human elk-L/Fc fusion proteins according to  claim 17 , wherein said proteins are joined by disulfide bonds.  
     
     
         22 . A method for treating a mammal afflicted with an injury to or disorder of neural tissue, comprising administering to said mammal an effective amount of a dimer of  claim 21 .  
     
     
         23 . A method of  claim 22 , wherein said injury or disorder is mediated or characterized at least in part by excitotoxicity.  
     
     
         24 . A pharmaceutical composition comprising an effective amount of an elk-L protein of  claim 10  and a suitable diluent, excipient, or carrier.  
     
     
         25 . A pharmaceutical composition comprising an effective amount of a dimer of  claim 21  and a suitable diluent, excipient, or carrier.  
     
     
         26 . An isolated nucleic acid molecule comprising a sequence of at least about 14 nucleotides of the DNA sequence presented in SEQ ID NO:1 or its DNA or RNA complement.