Extracellular/epidermal growth factor-like protein

Abstract

The present invention discloses an extracellular/epidermal growth factor polypeptides and polynucleotides encoding such polypeptides. Also provided is a procedure for producing such polypeptides by recombinant techniques and therapeutic uses of the polypeptides which include induction of DNA synthesis, stimulating wound healing, treating neurological disorders, treating ocular disorders, treating kidney and liver disorders and stimulating embryogenesis and angiogenesis. Also disclosed are antagonists against such polypeptide and their use as a therapeutic to treat neoplasia. Also disclosed are diagnostic assays for detecting altered levels of the polypeptide of the present invention and mutations in the nucleic acid sequences which encode the polypeptides of the present invention.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a polynucleotide having at least a 95% identity to a member selected from the group consisting of: 
 (a) a polynucleotide encoding a polypeptide comprising an amino acid sequence set forth in SEQ ID NO:2 or the polypeptide encoding by ATCC Deposit No. ______;    (b) a polynucleotide encoding a polypeptide comprising an amino acid sequence set forth as residues 57 to 448 in SEQ ID NO:2 or as encoded by ATCC Deposit No. 97285;    (c) a polynucleotide encoding the mature EEGF polypeptide shown as residues 26 to 448 in SEQ ID NO:2 or as encoded by ATCC Deposit No. ______;    (d) a polynucleotide encoding the EGF-1 domain of EEGF shown as residues 112-153 of SEQ ID NO:2;    (e) a polynucleotide encoding the EGF-2 domain of EEGF shown as residues 154-190 of SEQ ID NO:2;    (f) a polynucleotide encoding the EGF-3 domain of EEGF shown as residues 191-230 of SEQ ID NO:2;    (g) a polynucleotide encoding the EGF-4 domain of EEGF shown as residues 231-271 of SEQ ID NO:2;    (h) a polynucleotide encoding the EGF-5 domain of EEGF shown as residues 272-314; and    (i) a polynucleotide which is complementary to the polynucleotide of (a), (b), (c), (d), (e), (f), (g) or (h).    
     
     
         2 . The polynucleotide of    claim 1    wherein the polynucleotide is DNA.  
     
     
         3 . The polynucleotide of    claim 1    wherein the polynucleotide is RNA.  
     
     
         4 . The polynucleotide of    claim 1    comprising nucleotide 286 to nucleotide 1554 of SEQ ID NO:1.  
     
     
         5 . The polynucleotide of    claim 1    comprising nucleotide 211 to nucleotide 1554 of SEQ ID NO:1.  
     
     
         6 . A vector comprising the DNA of    claim 2   .  
     
     
         7 . A host cell comprising the vector of    claim 6   .  
     
     
         8 . A process for producing a polypeptide comprising: expressing from the host cell of    claim 7    the polypeptide encoded by said DNA.  
     
     
         9 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of    claim 6   .  
     
     
         10 . A polypeptide comprising an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group comprising: 
 (a) the amino acid sequence of the complete EEGF polypeptide set forth in SEQ ID NO:2, or the amino acid sequence of the polypeptide encoded by the cDNA contained in ATCC Deposit No. ______;    (b) the amino acid sequence of the EEGF polypeptide set forth in SEQ ID NO:2 as residues 57 to 448, or the amino acid sequence of the polypeptide encoded by the cDNA contained in ATCC Deposit No. 97285;    (c) the amino acid sequence of the mature EEGF polypeptide set forth as residues 26 to 448 in SEQ ID NO:2, or the amino acid sequence of the mature EEGF polypeptide encoded by ATCC Deposit No. ______;    (d) the amino acid sequence of the EGF-1 domain of EEGF shown as residues 112-153 in SEQ ID NO:2;    (e) the amino acid sequence of the EGF-2 domain of EEGF shown as residues 154-190 in SEQ ID NO:2;    (f) the amino acid sequence of the EGF-3 domain of EEGF shown as residues 191-230 in SEQ ID NO:2;    (g) the amino acid sequence of the EGF-4 domain of EEGF shown as residues 231-271 in SEQ ID NO:2; and    (h) the amino acid sequence of the EGF-5 domain of EEGF shown as residues 272-314 in SEQ ID NO:2.    
     
     
         11 . An antibody against the polypeptide of    claim 10   .  
     
     
         12 . An antagonist for the polypeptide of    claim 10   .  
     
     
         13 . A method for the treatment of a patient having need of EEGF comprising: administering to the patient a therapeutically effective amount of the polypeptide of    claim 10   .  
     
     
         14 . A method for the treatment of a patient having need to inhibit EEGF comprising: administering to the patient a therapeutically effective amount of the antagonist of    claim 12   .  
     
     
         15 . The method of    claim 14    wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo.  
     
     
         16 . A process for identifying compounds active as antagonists to the polypeptide of    claim 10    comprising: contacting a reaction mixture containing a cell type which expresses the EEGF receptor and a compound to be screened; and detecting the absence of a signal generated from said receptor after binding of said compound to identify if the compound is an effective antagonist.  
     
     
         17 . A process for diagnosing a disease or a susceptibility to a disease comprising: determining a mutation in the polynucleotide of    claim 1   .  
     
     
         18 . A diagnostic process comprising: analyzing for the presence of the polypeptide of    claim 10    in a sample.