Density enhanced protein tyrosine phosphatases

Abstract

Novel Type III density enhanced protein tyrosine phosphatases are disclosed and exemplified by human DEP-1 enzyme. Polynucleotides encoding huDEP-1 are disclosed, along with methods and materials for production of the same by recombinant procedures. Binding molecules specific for DEP-1 are also disclosed as useful for modulating the biological activities of DEP-1.

1 . (canceled)  
     
     
         2 . An immunogen selected from: 
 (a) a polypeptide that comprises the amino acid sequence set forth in SEQ ID NO:2;    (b) a polypeptide that comprises a human Type III density enhanced protein-1 tyrosine phosphatase polypeptide that is encoded by a DNA molecule that hybridizes at 65° C. in a buffer containing 40 mM Na 2 HPO 4 , 1% SDS, and 1 mM EDTA to the complement of the protein coding portions of the DNA sequence set forth in SEQ ID NO: 1;    (c) a polypeptide consisting of the extracellular region polypeptide of 940 consecutive amino acids of SEQ ID NO:2, said extracellular region polypeptide comprising an amino acid sequence with an amino terminus of Gly located at residue 37 of SEQ ID NO:2; and    (d) a huDEP-1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, wherein said huDEP-1 polypeptide is present on the extracellular membrane surface of a cell;    (e) a polypeptide that comprises an intracellular portion of 341 amino acids of a human Type III density enhanced protein-1 tyrosine phosphatase polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, wherein the intracellular portion comprises amino acids residues 1060-1296 of SEQ ID NO:2, and wherein the intracellular portion does not include amino acids 977-996 of SEQ ID NO:2; and    (f) a polypeptide that comprises an amino acid sequence as set forth at positions 997-1337 of SEQ ID NO:2;    (g) a polypeptide fragment comprising an amino acid sequence as set forth at positions 977-996 of SEQ ID NO:2;    (h) a polypeptide fragment comprising an amino acid sequence as set forth at positions 1060-1296 of SEQ ID NO:2    (i) a polypeptide fragment comprising an amino acid sequence as set forth at positions 1297-1315 of SEQ ID NO:2; and    (j) a polypeptide fragment comprising an amino acid sequence as set forth at positions 1321-1334 of SEQ ID NO:2.    
     
     
         3 - 11 . (canceled)  
     
     
         12 . A method for generating an antibody that specifically binds to a polypeptide that comprises the amino acid sequence as set forth in SEQ ID NO:2, comprising immunizing an animal with the immunogen according to  claim 2 .  
     
     
         13 - 15 . (canceled)  
     
     
         16 . An antibody that specifically binds to a human Type III density enhanced protein-1 tyrosine phosphatase polypeptide that is encoded by a DNA molecule that hybridizes at 65° C. in a buffer containing 40 mM Na 2 HPO 4 , 1% SDS, and 1 mM EDTA to the complement of the protein coding portions of the DNA sequence set forth in SEQ ID NO:1.  
     
     
         17 . An antibody that specifically binds to a polypeptide fragment: 
 (a) a polypeptide fragment comprising an intracellular portion of 341 amino acids of a human Type III density enhanced protein-1 tyrosine phosphatase polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, wherein the intracellular portion comprises amino acids residues 1060-1296 of SEQ ID NO:2, and wherein the intracellular portion does not include amino acids 977-996 of SEQ ID NO:2;    (b) a polypeptide fragment comprising the amino acid sequence as set forth at positions 997-1337 of SEQ ID NO:2;    (c) a polypeptide fragment comprising the amino acid sequence as set forth at positions 977-996 of SEQ ID NO:2;    (d) a polypeptide fragment comprising the amino acid sequence as set forth at positions 1060-1296 of SEQ ID NO:2;    (e) a polypeptide fragment comprising the amino acid sequence as set forth at positions 1297-1315 of SEQ ID NO:2; and    (f) a polypeptide fragment comprising the amino acid sequence as set forth at positions 1321-1334 of SEQ ID NO:2.    
     
     
         18 . The antibody according to either  claim 16  or  claim 17  wherein the antibody comprises (a) a polyclonal antibody; (b) a monoclonal antibody; (c) a chimeric antibody; (d) a single chain antibody; or (e) a CDR-grafted antibody.  
     
     
         19 - 24 . (canceled)  
     
     
         25 . A cell line that produces the antibody according to either  claim 16  or  claim 17 .  
     
     
         26 . The cell line according to  claim 25 , wherein the cell line is a hybridoma cell line.  
     
     
         27 . A method for detecting the presence of a human Type III density enhanced protein-1 tyrosine phosphatase polypeptide (huDEP-1) in a cell, comprising: 
 (a) contacting at least one cell or a lysate of said cell with an antibody according to either  claim 16  or  claim 17 , wherein said cell comprises a huDEP-1 polypeptide comprising the sequence set forth in SEQ ID NO:2, under conditions and for a time sufficient to allow formation of an antibody/huDEP-1 complex; and    (b) detecting the antibody/huDEP-1 complex, and therefrom detecting the presence of the huDEP-1 polypeptide in the cell.    
     
     
         28 . The method according to  claim 27 , wherein the cell is obtained from a human.  
     
     
         29 - 42 . (canceled)