METHODS OF MODULATING CELLULAR ACTIVITY INVOLVING SPHINGOSINE KINASE AND AGENTS FOR SAME, AND SPHINGOSINE KINASE VARIANTS

摘要

The present invention relates generally to a method of modulating cellular activity and to agents for use therein. More particularly, the present invention provides a method of modulating cellular activity by modulating intracellular translocation of sphingosine kinase to the cell membrane. In a related aspect, the present invention provides a method of modulating sphingosine kinase mediated signalling via modulation of its intracellular translocation and agents for use therein. The present invention still further extends to sphingosine kinase variants and to functional derivatives, homologues and analogues thereof, exhibiting ablated or reduced capacity to undergo translocation. The method and molecules of the present invention are useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate cellular functional activity and/or aberrant, unwanted or otherwise inappropriate sphingosine kinase mediated signalling. The present invention is further directed to methods for identifying and/or designing agents capable of modulating sphingosine kinase intracellular translocation.