Neukinase, a downstream protein of neuregulin

Abstract

The present invention relates to neukinase, a downstream protein kinase in the neuregulin signaling pathway. In certain aspects, the present invention provides isolated neukinase-encoding nucleic acids, neukinase polypeptides, oligonucleotides that hybridize to neukinase nucleic acids, and expression vectors containing neukinase-encoding sequences. The present invention further provides isolated host cells, antibodies, transgenic non-human animals, compositions, and kits relating to neukinase. In other aspects, the present invention further provides methods of identifying predisposition to cardiac dysfunction, methods of detecting the presence of neukinase, neukinase nucleic acid, methods of screening for agents which affect neukinase activity, and methods of modulating neukinase activity.

1 - 76 . (canceled) 
     
     
         77 . A method of detecting a genetic lesion in a neukinase gene one or more cardiac cell(s) of a subject, comprising: (a) isolating nucleic acid from one or more cardiac cell(s) of the subject, and (b) detecting the presence of a genetic lesion or lesions in the neukinase gene of said sample. 
     
     
         78 . The method of  claim 77 , wherein said genetic lesion in the neukinase gene is detected by determining the presence of: a deletion of one or more nucleotides from the neukinase gene, an addition of one or more nucleotides to the neukinase gene, a substitution of one or more nucleotides in the neukinase gene, a chromosomal rearrangement of the neukinase gene, an alteration in neukinase mRNA transcript levels, aberrant modification of the neukinase gene, a change in methylation of the neukinase gene, or a non-wild-type splicing pattern of neukinase mRNA transcripts. 
     
     
         79 . A method of detecting abnormal levels of neukinase gene expression in one or more cardiac cell(s) of a subject, comprising (a) obtaining a biological sample comprising one or more cardiac cells of the subject, and (b) determining the levels of neukinase mRNA in said biological sample relative to a control sample, wherein abnormal levels of neukinase gene expression are detected if neukinase mRNA levels are higher or lower in said biological sample relative to the control sample. 
     
     
         80 . The method of  claim 79 , wherein the control sample is comprised of one or more healthy human cardiac cells. 
     
     
         81 . The method of  claim 79 , wherein abnormal levels of neukinase gene expression are detected if neukinase mRNA levels are higher in the biological sample relative to the control sample. 
     
     
         82 . The method of  claim 79 , wherein abnormal levels of neukinase gene expression are detected if neukinase mRNA levels are lower in the biological sample relative to the control sample. 
     
     
         83 . An antibody that specifically binds to an isolated polypeptide, wherein the isolated polypeptide comprising an amino acid sequence having at least 70% identity to SEQ ID NO:1, SEQ ID NO:2 or SEQ ID NO:25, wherein the polypeptide is capable of phosphorylating myosin light chain.