Abstract: The present invention relates generally to a sphingosine kinase variant and to derivatives, analogues, chemical equivalents and mimetics thereof exhibiting reduced catalytic activity and, more particularly, to sphingosine kinase variants which exhibit a reduced capacity to phosphorylate sphingosine to sphingosine-1-phosphate. The present invention also contemplates genetic sequences encoding said sphingosine kinase variants and derivatives, analogues and mimetics thereof. The variants of the present invention are useful in a range of therapeutic and prophylactic applications.

Abstract: The present invention relates generally to a method of modulating cytokine-mediated cellular activity and to agents useful for same. More particularly, the present invention contemplates a method of modulating tumor necrosis factor-mediated cellular activity by modulating an intracellular sphingosine kinase-dependent signalling mechanism. The method of the present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate cytokine-mediated cellular activity The present invention is further directed to methods for identifying and/or designing agents capable of modulating the subject sphingosine kinase-dependent signalling mechanism.