Methods and products relating to gsk3ss regulation

Abstract

The invention relates to methods and compositions for regulation of GSK3β activity. The invention provides phosphorylated GSK3β polypeptides and antibodies that recognize such polypeptides. The invention further includes methods for treating disorders that are associated with elevated or reduced GSK3β activity.

1 . An isolated GSK3β polypeptide, wherein the polypeptide is a full-length GSK3β protein or is a fragment of a full-length GSK3β protein and comprises a phosphorylated residue that corresponds to residue Thr 390  in a full-length, wild-type, human GSK3β amino acid sequence, or corresponds to residue Ser 389  in a full-length, wild-type, mouse GSK3β amino acid sequence. 
     
     
         2 . The isolated GSK3β polypeptide of  claim 1 , wherein the GSK3β polypeptide is a human GSK3β polypeptide. 
     
     
         3 . The isolated GSK3β polypeptide of  claim 1 , wherein the phosphorylated residue corresponds to the Thr 390  residue. 
     
     
         4 . The isolated GSK3β polypeptide of  claim 3 , wherein the polypeptide comprises the amino acid sequence set forth as: RIQAAAST(PO 3 H 2 )PTN (SEQ ID NO:7). 
     
     
         5 . A composition comprising the isolated GSK3β polypeptide of  claim 1 . 
     
     
         6 . The composition of  claim 5 , further comprising a pharmaceutically acceptable carrier. 
     
     
         7 . A fusion protein comprising the GSK3β polypeptide of  claim 1 . 
     
     
         8 . A method of producing an antibody that specifically binds to a phosphorylated GSK3β polypeptide, the method comprising,
 inoculating an animal with a polypeptide of  claim 1 , that comprises a phosphorylated residue that corresponds to residue Thr 390  in a full-length, wild-type, human GSK3β amino acid sequence, or corresponds to residue Ser 389  in a full-length, wild-type, mouse GSK3β amino acid sequence, wherein the polypeptide elicits an immune response in the animal to produce the antibody; and 
 isolating the antibody from the animal; wherein the antibody specifically binds to a phosphorylated GSK3β polypeptide. 
 
     
     
         9 . The method of  claim 8 , wherein the polypeptide comprises the amino acid sequence set forth as RIQAAAST(PO 3 H 2 )PTN (SEQ ID NO:7). 
     
     
         10 . The method of  claim 8 , wherein the polypeptide comprises a threonine residue that corresponds to residue Thr 390  of full-length, wild-type, human GSK3β polypeptide. 
     
     
         11 . A method of reducing activity of GSK3β in a cell, the method comprising:
 contacting the cell with a composition comprising an isolated GSK3β polypeptide, wherein the polypeptide is a full-length GSK3β protein or a fragment of a full-length GSK3β protein and comprises a phosphorylated residue that corresponds to residue Thr 390  in a full-length, wild-type, human GSK3β amino acid sequence, or corresponds to residue Ser 389  in a full-length, wild-type, mouse GSK3β amino acid sequence. 
 
     
     
         12 . The method of  claim 11 , wherein the GSK3β polypeptide is a human GSK3β polypeptide. 
     
     
         13 . The method of  claim 11 , wherein the phosphorylated residue corresponds to the Thr 390  residue. 
     
     
         14 . The method of  claim 11 , wherein the polypeptide comprises the amino acid sequence set forth as: RIQAAAST(PO 3 H 2 )PTN (SEQ ID NO:7). 
     
     
         15 . A method for treating a disease or condition associated with GSK3β activity, the method comprising:
 administering to a subject having a disease or condition associated with GSK3β activity a therapeutically effective amount of a composition comprising a GSK3β polypeptide, wherein the polypeptide is a full-length GSK3β protein or a fragment of a full-length GSK3β protein and comprises a phosphorylated residue that corresponds to residue Thr 390  in a full-length, wild-type, human GSK3β amino acid sequence, or corresponds to residue Ser 389  in a full-length, wild-type, mouse GSK3β amino acid sequence. 
 
     
     
         16 . The method of  claim 15 , wherein the GSK3β polypeptide is a human GSK3β polypeptide. 
     
     
         17 . The method of  claim 15 , wherein the phosphorylated residue corresponds to the Thr 390  residue. 
     
     
         18 . The method of  claim 15 , wherein the polypeptide comprises the amino acid sequence set forth as: RIQAAAST(PO 3 H 2 )PTN (SEQ ID NO:7). 
     
     
         19 . The isolated GSK3β polypeptide of  claim 1 , wherein the polypeptide is a fragment of a full-length GSK3β protein. 
     
     
         20 . The method of  claim 8 , wherein the polypeptide is a fragment of a full-length GSK3β protein.