Sphingosine kinase enzyme

Abstract

The present invention relates generally to novel protein molecules and to derivatives, analogues, chemical equivalents and mimetics thereof capable of modulating cellular activity and, in particular, modulating cellular activity via the modulation of signal transduction. More particularly, the present invention relates to human sphingosine kinase and to derivatives, analogues, chemical equivalents and mimetics thereof. The present invention also contemplates genetic sequences encoding said protein molecules and derivatives, analogues, chemical equivalents and mimetics thereof. The molecules of the present invention are useful in a range of therapeutic, prophylactic and diagnostic applications.

1 . A method of modulating the functional activity of sphingosine kinase in a mammal, said method comprising administering to said mammal a modulating effective amount of an agent for a time and under conditions sufficient to increase or decrease sphingosine kinase activity.  
     
     
         2 . A method of modulating cellular function activity in a mammal said method comprising administering to said mammal an effective amount of an agent for a time under conditions sufficient to modulate the expression of sphingosine kinase or sufficient to modulate the activity of sphingosine kinase.  
     
     
         3 . A method of modulating cellular functional activity in a mammal, said method comprising administering to said mammal an effective amount of a sphingosine kinase protein or a derivative, analogue, chemical equivalent or mimetic thereof, for a time and under conditions sufficient to modulate the functional activity of said cell, said protein optionally 
 being a human sphingosine kinase protein; or    comprising an amino acid sequence substantially as set forth in <400>2 or a derivative or mimetic thereof or a sequence having at least about 45% similarity to at least 10 contiguous amino acids in <400>2 or a derivative, analogue, chemical equivalent or mimetic or said protein; or    being encoded by a nucleotide sequence substantially as set forth in <400>1 or a derivative or analogue thereof or capable of hybridizing to <400>1 or <400>2 under low stringency conditions or a derivative, analogue, chemical equivalent or mimetic or said protein.    
     
     
         4 . A method of modulating cellular function activity in a mammal, said method comprising administering to said mammal an effective amount of an isolated nucleic acid molecule or derivative or analogue thereof comprising a nucleotide sequence encoding or complementary to a sequence encoding a novel sphingosine kinase protein or a derivative of mimetic of said sphingosine kinase protein, or a derivative, analogue, chemical equivalent or mimetic thereof for a time and under conditions sufficient to modulate the functional activity of said cell, said nucleic acid molecule optionally 
 being a human sphingosine kinase protein; or    comprising a nucleotide sequence encoding, or a nucleotide sequence complementary to a nucleotide sequence encoding, an amino acid sequence substantially as set forth in <400>2 or a derivative or mimetic thereof or having at least about 45% or greater similarity to at least 10 contiguous amino acids in <400>2; or    comprising a nucleotide sequence substantially as set forth in <400>1 or a derivative thereof capable of hybridizing to <400>1 under low stringency conditions; or    which further encodes an amino acid sequence corresponding to an amino acid sequence set forth in <400>2 or a sequence having at least about 45% similarity to at least 10 contiguous amino acids in <400>2, or <400>1.    
     
     
         5 . A method of modulating cellular functional activity in a mammal said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of sphingosine kinase or sufficient to modulate the activity of sphingosine kinase wherein said sphingosine kinase expression product or sphingosine kinase modulates the activity of said cell.  
     
     
         6 . A method of treating a mammal said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the expression of sphingosine kinase wherein said modulation results in modulation of cellular functional activity.  
     
     
         7 . A method of treating a mammal said method comprising administering to said mammal an effective amount of an agent for a time and under conditions sufficient to modulate the activity of sphingosine kinase wherein said modulation results in modulation of cellular functional activity.  
     
     
         8 . A method of treating a mammal, said method comprising administering to said mammal an effective amount of a protein as recited in  claim 15  or a derivative, analogue, chemical equivalent or mimetic thereof for a time and under conditions sufficient to modulate cellular functional activity.  
     
     
         9 . A method of treating a mammal said method comprising administering to said mammal an effective amount of a nucleic acid molecule as recited in  claim 16  or a derivative, analogue, chemical equivalent or mimetic thereof for a time and under conditions sufficient to modulate cellular functional activity.  
     
     
         10 . An agent for use in modulating sphingosine kinase activity or a derivative, analogue chemical equivalent or mimetic thereof wherein modulating said sphingosine kinase activity modulates cellular functional activity; or an agent for use in modulating sphingosine kinase expression or a derivative, analogue, chemical equivalent or mimetic thereof wherein modulating expression of said sphingosine kinase modulates cellular functional activity.  
     
     
         11 . An isolated antibody directed to the protein recited in  claim 15 .  
     
     
         12 . An isolated antibody directed to the nucleic acid molecule recited in  claim 16 .  
     
     
         13 . The antibody according to  claim 12  wherein said antibody is monoclonal antibody.  
     
     
         14 . The antibody according to  claim 11  wherein said antibody is monoclonal antibody.  
     
     
         15 . The antibody according to  claim 11  wherein said antibody is a polyclonal antibody.  
     
     
         16 . The antibody according to  claim 12  wherein said antibody is a polyclonal antibody.  
     
     
         17 . A method of diagnosing or monitoring a mammalian disease condition said method comprising screening for sphingosine kinase or sphingosine kinase in a biological sample isolated from said mammal.  
     
     
         18 . An isolated polypeptide, the polypeptide comprising at least 30 contiguous amino acid residues of amino acid residues 1 to 105 of SEQ ID NO: 2.  
     
     
         19 . An isolated polypeptide, the polypeptide comprising at least 50 contiguous amino acid residues of amino acid residues 1 to 105 of SEQ ID NO: 2.  
     
     
         20 . A composition comprising the polypeptide of  claim 18 , together with one or more pharmaceutically acceptable carriers and/or diluents.