Human heme-regulated initiation factor 2-alpha kinase

Abstract

The present invention provides an isolated nucleic acid sequence encoding a human heme-regulated initiation factor 2 alpha kinase. In addition, the invention provides a method for inhibiting protein synthesis, inducing cellular differentiation, or inhibiting infection in human cells by administering an effective amount of a heme-regulated initiation factor 2 alpha kinase to the cells. Methods are also provided for modulating heme-regulated initiation factor 2 alpha kinase activity and determining the level of heme-regulated initiation factor 2 alpha kinase expression.

What is claimed:  
     
         1 . An isolated antisense nucleic acid molecule, wherein the antisense nucleic acid molecule is complimentary to a nucleic acid molecule comprising: 
 a nucleic acid sequence according to SEQ ID NO:1;    a nucleic acid sequence which encodes the amino acid sequence according to SEQ ID NO:2; or    a nucleic acid molecule having at least 90% amino acid sequence identity to a nucleic acid sequence according to SEQ ID NO:1.    
     
     
         2 . A fragment of a nucleic acid molecule wherein the nucleic acid molecule comprises: 
 a nucleic acid sequence according to SEQ ID NO:1;    a nucleic acid sequence which encodes an amino acid sequence according to SEQ ID NO:2; or    a nucleic acid molecule having at least 90% amino acid sequence identity to a nucleic acid sequence according to SEQ ID NO:1, wherein the fragment specifically hybridizes to a nucleic acid molecule encoding human heme-regulated initiation factor 2 alpha kinase.    
     
     
         3 . The fragment according to  claim 2 , wherein the fragment is between 15 and 100 nucleotides in length.  
     
     
         4 . A transgenic animal wherein the animal has altered expression of heme-regulated initiation factor 2 alpha kinase.  
     
     
         5 . The transgenic animal according to  claim 4 , wherein the expression of heme-regulated initiation factor 2 alpha kinase is increased.  
     
     
         6 . The transgenic animal according to  claim 4 , wherein the expression of heme-regulated initiation factor 2 alpha kinase is decreased.  
     
     
         7 . A recombinant cell with decreased heme-regulated initiation factor 2 alpha kinase activity.  
     
     
         8 . The recombinant cell according to  claim 7 , wherein the cell produces an antisense RNA which is complimentary to a portion of the RNA encoding heme-regulated initiation factor 2 alpha kinase.  
     
     
         9 . An isolated protein encoded by a nucleic acid molecule, wherein the nucleic acid molecule comprises: 
 a nucleic acid sequence according to SEQ ID NO:1;    a nucleic acid sequence which encodes the amino acid sequence according to SEQ ID NO:2; or    a nucleic acid molecule having at least 90% amino acid sequence identity to a nucleic acid sequence according to SEQ ID NO:1.    
     
     
         10 . The protein according to  claim 9 , wherein the protein has heme-regulated initiation factor 2 alpha kinase activity.  
     
     
         11 . A fragment of the protein according to  claim 9 .  
     
     
         12 . The fragment according to  claim 11 , wherein the fragment comprises active sites of heme-regulated initiation factor 2 alpha kinase.  
     
     
         13 . An antibody specific to the protein according to  claim 9 .  
     
     
         14 . The antibody according to  claim 13 , wherein the antibody is a monoclonal antibody.  
     
     
         15 . The antibody according to  claim 13 , wherein the antibody is a polyclonal antibody.  
     
     
         16 . A pharmaceutical composition comprising heme-regulated initiation factor 2 alpha kinase in combination with a suitable pharmaceutical carrier for administration to cells.  
     
     
         17 . The pharmaceutical composition according to  claim 16 , wherein the kinase consists of the amino acid sequence of SEQ ID NO:2.  
     
     
         18 . A method for inhibiting protein synthesis, inducing cellular differentiation, or inhibiting infection in human cells, comprising: 
 administering to cells to be treated an effective amount of a heme-regulated initiation factor 2 alpha kinase in combination with a suitable pharmaceutical carrier for administration to the cells.    
     
     
         19 . A method for modulating heme-regulated initiation factor 2 alpha kinase activity, comprising: 
 administering to cells to be treated an effective amount of an antibody or a receptor protein which binds to heme-regulated eukaryotic initiation factor 2 alpha kinase in combination with a suitable pharmaceutical carrier for administration to the cells.