Novel human protein kinases

Abstract

The present invention provides novel human protein kinases (HPK) and polynucleotides which identify and encode HPK. The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding HPK. The invention also provides for pharmaceutical compositions comprising HPK or antagonists of HPK, and antibodies which specifically bind HPK. Additionally, the invention provides antisense molecules to HPK for treatment or prevention of diseases associated with abnormal expression of HPK.

What is claimed is:  
     
         1 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 a) an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3, or SEQ ID NO: 5,    b) a naturally-occurring amino acid sequence having at least 90% sequence identity to the amino acid sequence of a),    c) a biologically-active fragment of the amino acid sequence of a), and    d) an immunogenic fragment of the amino acid sequence of a).    
     
     
         2 . A polypeptide of  claim 1 , comprising the amino acid sequence of SEQ ID NO: 3.  
     
     
         3 . A polypeptide of  claim 1 , comprising the amino acid sequence of SEQ ID NO: 5.  
     
     
         4 . An isolated polynucleotide encoding a polypeptide of  claim 1 .  
     
     
         5 . An isolated polynucleotide of  claim 4 , having a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, and SEQ ID NO: 6.  
     
     
         6 . A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of  claim 4 .  
     
     
         7 . A cell transformed with a recombinant polynucleotide of  claim 6 .  
     
     
         8 . A method for producing a polypeptide of  claim 1 , the method comprising: 
 a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide, and said recombinant polynucleotide comprises a promoter sequence operably linked to a polynucleotide encoding the polypeptide of  claim 1 , and    b) recovering the polypeptide so expressed.    
     
     
         9 . A method of  claim 8 , wherein the polypeptide has the sequence of SEQ ID NO: 5.  
     
     
         10 . An isolated antibody which specifically binds to a polypeptide of  claim 1 .  
     
     
         11 . An isolated polynucleotide comprising a sequence selected from the group consisting of: 
 a) a polynucleotide sequence of SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 6,    b) a naturally-occurring polynucleotide sequence having at least 90% sequence identity to the polynucleotide sequence of a),    c) a polynucleotide sequence complementary to a),    d) a polynucleotide sequence complementary to b) and    e) a ribonucleotide equivalent of a)-d).    
     
     
         12 . An isolated polynucleotide comprising at least 60 contiguous nucleic acids of  claim 11 .  
     
     
         13 . A method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of  claim 11 , the method comprising: 
 a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and    b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof.    
     
     
         14 . A method of  claim 13 , wherein the probe comprises at least 60 contiguous nucleotides.  
     
     
         15 . A method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of  claim 11 , the method comprising: 
 a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and    b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof.    
     
     
         16 . A composition comprising an effective amount of a polypeptide of  claim 1  and an acceptable excipient.  
     
     
         17 . A composition of  claim 16 , wherein the polypeptide has the sequence of SEQ ID NO: 3  
     
     
         18 . A composition of  claim 16 , wherein the polypeptide has the sequence of SEQ ID NO: 5.  
     
     
         19 . A method for screening a compound for effectiveness as an agonist of a polypeptide of  claim 1 , the method comprising: 
 a) exposing a sample comprising a polypeptide of  claim 1  to a compound, and    b) detecting agonist activity in the sample.    
     
     
         20 . A method for screening a compound for effectiveness as an antagonist of a polypeptide of  claim 1 , the method comprising: 
 a) exposing a sample comprising a polypeptide of  claim 1  to a compound, and    b) detecting antagonist activity in the sample.    
     
     
         22 . A method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence of  claim 1 , the method comprising: 
 a) exposing a sample comprising the target polynucleotide to a compound, under conditions suitable for the expression of the target polynucleotide,    b) detecting altered expression of the target polynucleotide, and    c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound.    
     
     
         23 . A method for assessing toxicity of a test compound, said method comprising: 
 a) treating a biological sample containing nucleic acids with the test compound;    b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide of  claim 11  under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide comprising a polynucleotide sequence of a polynucleotide of  claim 11  or fragment thereof;    c) quantifying the amount of hybridization complex; and    d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound.