Transforming growth factor alpha hii

Abstract

The present invention discloses transforming growth factor alpha HII 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 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 polypeptides 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.

1 . An isolated polynucleotide comprising a member selected from the group consisting of:
 (a) a polynucleotide encoding a polypeptide comprising amino acids 1 to 374 of SEQ NO ID:2;   (b) a polynucleotide encoding a polypeptide comprising amino acids 2 to 374 of SEQ NO ID:2;   (c) a polynucleotide encoding a polypeptide comprising amino acids 46 to 374 of SEQ NO ID:2;   (d) a polynucleotide encoding a polypeptide comprising amino acids 215 to 374 of SEQ NO ID:2;   (e) a polynucleotide encoding a polypeptide comprising amino acids 1 to 264 of SEQ NO ID:2;   (f) a polynucleotide encoding a polypeptide comprising amino acids 46 to 264 of SEQ NO ID:2;   (g) a polynucleotide encoding a polypeptide comprising amino acids 215 to 264 of SEQ NO ID:2;   (h) a polynucleotide encoding at least 30 contiguous amino acids of SEQ NO ID:2;   (i) a polynucleotide encoding at least 50 contiguous amino acids of SEQ NO ID:2;   (j) a polynucleotide capable of hybridizing to the polynucleotide of (a), (b), (c), (d), (e), (f), or (g);   (k) a polynucleotide which is at least 70% identical to the polynucleotide of (a), (b), (c), (d), (e), (f), or (g); and   (l) a polynucleotide fragment of the polynucleotide of (a), (b), (c), (d), (e), (f), or (g).   
     
     
         2 . The isolated polynucleotide of  claim 1  wherein the polynucleotide is DNA. 
     
     
         3 . The isolated polynucleotide of  claim 1  wherein the polynucleotide is RNA. 
     
     
         4 . The isolated polynucleotide of  claim 1  wherein the polynucleotide is genomic DNA. 
     
     
         5 . The isolated polynucleotide of  claim 1  encoding the polypeptide comprising amino acids 1 to 374 as set forth in SEQ ID NO:2. 
     
     
         6 . The isolated polynucleotide of  claim 1  encoding the polypeptide comprising amino acids 46 to 374 as set forth in SEQ ID NO:2. 
     
     
         7 . The isolated polynucleotide of  claim 1  encoding the polypeptide comprising amino acids 1 to 264 as set forth in SEQ ID NO:2. 
     
     
         8 . The isolated polynucleotide of  claim 1  encoding the polypeptide comprising amino acids 46 to 264 as set forth in SEQ ID NO:2. 
     
     
         9 . The isolated polynucleotide of  claim 1  encoding the polypeptide comprising amino acids 215 to 264 as set forth in SEQ ID NO:2. 
     
     
         10 . An isolated polynucleotide comprising a member selected from the group consisting of
 (a) a polynucleotide which encodes a mature polypeptide having the amino acid sequence expressed by the DNA contained in ATCC Deposit No. 97160;   (b) a polynucleotide capable of hybridizing to the polynucleotide of (a);   (c) a polynucleotide which is at least 70% identical to the polynucleotide of (a); and   (d) a polynucleotide fragment of the polynucleotide of (a), (b), or (c).   
     
     
         11 . The polynucleotide of  claim 1  having the sequence as set forth in SEQ ID NO:1. 
     
     
         12 . The polynucleotide of  claim 1  comprising nucleotide 323 to nucleotide 1114 as set forth in SEQ ID NO:1. 
     
     
         13 . The polynucleotide of  claim 1  comprising nucleotide 458 to nucleotide 1114 as set forth in SEQ ID NO:1. 
     
     
         14 . The polynucleotide of  claim 1  comprising nucleotide 965 to nucleotide 1114 as set forth in SEQ ID NO:1. 
     
     
         15 . A vector comprising the DNA of  claim 2 . 
     
     
         16 . A host cell transformed or transfected with the vector of  claim 15 . 
     
     
         17 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 16  the polypeptide encoded by said DNA. 
     
     
         18 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of  claim 15 . 
     
     
         19 . A polypeptide comprising a member selected from the group consisting of:
 (a) amino acids 1 to 374 of SEQ ID NO:2;   (b) amino acids 46 to 374 of SEQ ID NO:2;   (c) amino acids 1 to 264 of SEQ ID NO:2;   (d) amino acids 46 to 264 of SEQ ID NO:2;   (e) amino acids 215 to 264 of SEQ ID NO:2;   (f) a polypeptide encoded by the the cDNA contained in ATCC Deposit No. 97160;   (g) at least 30 contiguous amino acids of SEQ NO ID:2;   (h) at least 50 contiguous amino acids of SEQ NO ID:2;   (i) a polypeptide which is at least 70% identical to the polypeptide of (a), (b), (c), (d), (e), or (f); and   a polypeptide fragment of the polypeptide of (a), (b), (c), (d), (e), or (f).   
     
     
         20 . The polypeptide of  claim 19  comprising amino acids 215 to 264 of SEQ ID NO:2. 
     
     
         21 . An antibody against the polypeptide of  claim 19 . 
     
     
         22 . A compound which inhibits activation of the polypeptide of  claim 19 . 
     
     
         23 . A compound which activates the polypeptide of  claim 19 . 
     
     
         24 . A method for the treatment of a patient having need of TGFα-HII comprising: administering to the patient a therapeutically effective amount of the polypeptide of  claim 19 . 
     
     
         25 . A method for the treatment of a patient having need to inhibit TGFα-HII comprising: administering to the patient a therapeutically effective amount of the compound of  claim 22 . 
     
     
         26 . The method of  claim 24  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. 
     
     
         27 . A process for identifying compounds active as agonists to the polypeptide of  claim 19  comprising:
 contacting a reaction mixture containing a cell type which expresses a TGFα-HII receptor and a compound to be screened; and   determining if the compound generates a signal from said receptor to identify if the compound is an effective agonist.   
     
     
         28 . A process for identifying compounds active as antagonists to the polypeptide of  claim 19  comprising:
 contacting a reaction mixture containing a cell type which expresses the TGFα-HII 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.   
     
     
         29 . A process for diagnosing a disease or a susceptibility to a disease comprising: determining a mutation in the polynucleotide of  claim 1 . 
     
     
         30 . A diagnostic process comprising: analyzing for the presence of the polypeptide of  claim 19  in a sample derived from a host.