Novel sphingosine kinases

Abstract

Disclosed herein are novel human nucleic acid sequences that encode polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, and antibodies that immunospecifically-bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the aforementioned polypeptide, polynucleotide, or antibody. The invention further discloses therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of disorders involving any one of these novel human nucleic acids and proteins.

1 - 4 . (canceled)  
     
     
         5 . An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) a mature form of an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 6;    (b) a variant of a mature form of an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 6, wherein one or more amino acid residues in said variant differs from the amino acid sequence of said mature form, provided that said variant differs in no more than 15% of the amino acid residues from the amino acid sequence of said mature form;    (c) an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 6;    (d) a variant of an amino acid sequence selected from the group consisting of SEQ ID NOS:2 and 6, wherein one or more amino acid residues in said variant differs from the amino acid sequence of said mature form, provided that said variant differs in no more than 15% of amino acid residues from said amino acid sequence;    (e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising an amino acid sequence chosen from the group consisting of SEQ ID NOS:2 and 6, or a variant of said polypeptide, wherein one or more amino acid residues in said variant differs from the amino acid sequence of said mature form, provided that said variant differs in no more than 15% of amino acid residues from said amino acid sequence; and    (f) a nucleic acid molecule comprising the complement of (a), (b), (c), (d) or (e).    
     
     
         6 . The nucleic acid molecule of  claim 5 , wherein the nucleic acid molecule comprises the nucleotide sequence of a naturally-occurring allelic nucleic acid variant.  
     
     
         7 . The nucleic acid molecule of  claim 5 , wherein the nucleic acid molecule encodes a polypeptide comprising the amino acid sequence of a naturally-occurring polypeptide variant.  
     
     
         8 . The nucleic acid molecule of  claim 5 , wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 1 and 5.  
     
     
         9 . The nucleic acid molecule of  claim 5 , wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: 
 (a) a nucleotide sequence selected from the group consisting of SEQ ID NOS: 1 and 5;    (b) a nucleotide sequence differing by one or more nucleotides from a nucleotide sequence selected from the group consisting of SEQ ID NOS: 1 and 5, provided that no more than 20% of the nucleotides differ from said nucleotide sequence;    (c) a nucleic acid fragment of (a); and    (d) a nucleic acid fragment of (b).    
     
     
         10 . The nucleic acid molecule of  claim 5 , wherein said nucleic acid molecule hybridizes under stringent conditions to a nucleotide sequence chosen from the group consisting of SEQ ID NOS: 1 and 5, or a complement of said nucleotide sequence.  
     
     
         11 . The nucleic acid molecule of  claim 5 , wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: 
 (a) a first nucleotide sequence comprising a coding sequence differing by one or more nucleotide sequences from a coding sequence encoding said amino acid sequence, provided that no more than 20% of the nucleotides in the coding sequence in said first nucleotide sequence differ from said coding sequence;    (b) an isolated second polynucleotide that is a complement of the first polynucleotide; and    (c) a nucleic acid fragment of (a) or (b).    
     
     
         12 . A vector comprising the nucleic acid molecule of  claim 11 .  
     
     
         13 . The vector of  claim 12 , further comprising a promoter operably-linked to said nucleic acid molecule.  
     
     
         14 . A cell comprising the vector of  claim 12 .  
     
     
         15 - 18 . (canceled)  
     
     
         19 . A method for determining the presence or amount of the nucleic acid molecule of  claim 5  in a sample, the method comprising: 
 (a) providing the sample;    (b) contacting the sample with a probe that binds to said nucleic acid molecule; and    (c) determining the presence or amount of the probe bound to said nucleic acid molecule,    thereby determining the presence or amount of the nucleic acid molecule in said sample.    
     
     
         20 . The method of  claim 19  wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.  
     
     
         21 . The method of  claim 20  wherein the cell or tissue type is cancerous.  
     
     
         22 - 29 . (canceled)  
     
     
         30 . A method of treating or preventing a SphK-associated disorder, said method comprising administering to a subject in which such treatment or prevention is desired the nucleic acid of  claim 5  in an amount sufficient to treat or prevent said SphK-associated disorder in said subject.  
     
     
         31 . The method of  claim 30  wherein the disorder is a cell proliferative disorder selected from the group consisting of cancers, ischemia, or restenosis.  
     
     
         32 . The method of  claim 30  wherein administration is by catheter, stent, or syringe.  
     
     
         33 . The method of  claim 30 , wherein said subject is a human.  
     
     
         34 - 38 . (canceled)  
     
     
         39 . A pharmaceutical composition comprising the nucleic acid molecule of  claim 5  and a pharmaceutically-acceptable carrier.  
     
     
         40 - 41 . (canceled)  
     
     
         42 . A kit comprising in one or more containers, the pharmaceutical composition of  claim 39 .  
     
     
         43 - 45 . (canceled)  
     
     
         46 . A method for determining the presence of or predisposition to a disease associated with altered levels of the nucleic acid molecule of  claim 5  in a first mammalian subject, the method comprising: 
 (a) measuring the amount of the nucleic acid in a sample from the first mammalian subject; and    (b) comparing the amount of said nucleic acid in the sample of step (a) to the amount of the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease;    wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.    
     
     
         47 . The method of  claim 46  wherein the predisposition is to cancers.  
     
     
         48 . (canceled)  
     
     
         49 . A method of treating a pathological state in a mammal, the method comprising administering to the mammal an isolated nucleic acid in an amount that is sufficient to alleviate the pathological state, wherein the isolated nucleic acid is an isolated nucleic acid having an nculeic acid sequence at least 95% identical to a nucleic acid comprising a nucleic acid sequence of at least one of SEQ ID NOS: 2 and 6, or a compliment thereof  
     
     
         50 - 53 . (canceled)