Growth differentiation factor-15

Abstract

Growth differentiation factor-15 (GDF-15) polynucleotide sequence and amino acid sequence are provided herein. Also described are diagnostic and therapeutic methods of using GDF-15 polypeptide and polynucleotide sequences.

1 . Substantially pure growth differentiation factor-15 (GDF-15).  
     
     
         2 . An isolated polynucleotide sequence encoding the GDF-15 polypeptide of  claim 1 .  
     
     
         3 . An isolated polynucleotide selected from the group consisting of: 
 a) FIG. 1, wherein T can also be U;    b) nucleic acid sequences complementary to FIG. 1;    c) fragments of a) or b) that are at least 15 bases in length and that will selectively hybridize to DNA which encodes the GDF-15 polypeptide of FIG. 1.    
     
     
         4 . The polynucleotide sequence of  claim 2 , wherein the polynucleotide is isolated from a mammalian cell.  
     
     
         5 . The polynucleotide of  claim 4 , wherein the mammalian cell is selected from the group consisting of mouse, rat, and human cell.  
     
     
         6 . An expression vector including the polynucleotide of  claim 2 .  
     
     
         7 . The vector of  claim 6 , wherein the vector is a plasmid.  
     
     
         8 . The vector of  claim 6 , wherein the vector is a virus.  
     
     
         9 . A host cell stably transformed with the vector of  claim 6 .  
     
     
         10 . The host cell of  claim 9 , wherein the cell is prokaryotic.  
     
     
         11 . The host cell of  claim 9 , wherein the cell is eukaryotic.  
     
     
         12 . Antibodies that bind to the polypeptide of  claim 1  or fragments thereof.  
     
     
         13 . The antibodies of  claim 12 , wherein the antibodies are polyclonal.  
     
     
         14 . The antibodies of  claim 12 , wherein the antibodies are monoclonal.  
     
     
         15 . A method of detecting a cell proliferative disorder comprising contacting the antibody of  claim 12  with a specimen of a subject suspected of having a GDF-15 associated disorder and detecting binding of the antibody.  
     
     
         16 . The method of  claim 15 , wherein the detecting is in vivo.  
     
     
         17 . The method of  claim 16 , wherein the antibody is detectably labeled.  
     
     
         18 . The method of  claim 17 , wherein the detectable label is selected from the group consisting of a radioisotope, a fluorescent compound, a bioluminescent compound and a chemiluminescent compound.  
     
     
         19 . The method of  claim 15 , wherein the detection is in vitro.  
     
     
         20 . The method of  claim 19 , wherein the antibody is detectably labeled.  
     
     
         21 . The method of  claim 20 , wherein the label is selected from the group consisting of a radioisotope, a fluorescent compound, a bioluminescent compound, a chemoluminescent compound and an enzyme.  
     
     
         22 . A method of treating a cell proliferative disorder or immunologic disorder associated with expression of GDF-15, comprising contacting the cells with a reagent which suppresses the GDF-15 activity.  
     
     
         23 . The method of  claim 22 , wherein the reagent is an anti-GDF-15 antibody.  
     
     
         24 . The method of  claim 22 , wherein the reagent is a GDF-15 antisense sequence.  
     
     
         25 . The method of  claim 22 , wherein the reagent which suppresses GDF-15 activity is introduced to a cell using a vector.  
     
     
         26 . The method of  claim 25 , wherein the vector is a colloidal dispersion system.  
     
     
         27 . The method of  claim 26 , wherein the colloidal dispersion system is a liposome.  
     
     
         28 . The method of  claim 27 , wherein the liposome is essentially target specific.  
     
     
         29 . The method of  claim 28 , wherein the liposome is anatomically targeted.  
     
     
         30 . The method of  claim 29 , wherein the liposome is mechanistically targeted.  
     
     
         31 . The method of  claim 30 , wherein the mechanistic targeting is passive.  
     
     
         32 . The method of  claim 30 , wherein the mechanistic targeting is active.  
     
     
         33 . The method of  claim 32 , wherein the liposome is actively targeted by coupling with a moiety selected from the group consisting of a sugar, a glycolipid, and a protein.  
     
     
         34 . The method of  claim 33 , wherein the protein moiety is an antibody.  
     
     
         35 . The method of  claim 34 , wherein the vector is a virus.  
     
     
         36 . The method of  claim 35 , wherein the virus is an RNA virus.  
     
     
         37 . The method of  claim 36 , wherein the RNA virus is a retrovirus.  
     
     
         38 . The method of  claim 37 , wherein the retrovirus is essentially target specific.  
     
     
         39 . The method of  claim 38 , wherein a moiety for target specificity is encoded by a polynucleotide inserted into the retroviral genome.  
     
     
         40 . The method of  claim 38 , wherein a moiety for target specificity is selected from the group consisting of a sugar, a glycolipid, and a protein.  
     
     
         41 . The method of  claim 40 , wherein the protein is an antibody.  
     
     
         42 . A method for identifying a GDF-15 receptor polypeptide comprising: 
 a) incubating components comprising GDF-15 polypeptide and a cell expressing a receptor or a soluble receptor under conditions sufficient to allow the GDF-15 to bind to the receptor;    b) measuring the binding of the GDF-15 polypeptide to the receptor; and    c) isolating the receptor.