Abstract: The present invention relates to a method of modulating cellular activity. More particularly, the present invention provides a method of modulating apoptosis by modulating protein 14-3-3 phosphorylation and, thereby, its functionality. The present invention still further extends to methods for identifying agents capable of modulating protein 14-3-3 phosphorylation. The method and molecules of the present invention are useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by unwanted cellular activity, such as unwanted cell survival.

Abstract: The present invention relates to a method of modulating cellular activity. More particularly, the present invention provides a method of modulating apoptosis by modulating protein 14-3-3 phosphorylation and, thereby its functionality. The present invention still further extends to methods for identifying agents capable of modulating protein 14-3-3 phosphorylation. The method and molecules of the present invention are useful, inter alia, in the treatment and/or prophylaxis of conditions characterized by unwanted cellular activity, such as unwanted cell survival.

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 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.

Abstract: The invention relates to detection of sphingosine kinase activity and sphingosine kinase agonist or antagonist activity.

Abstract: The present invention relates generally to a method of modulating smooth muscle cell functioning and agents useful for same. More particularly, the present invention relates to a method of modulating smooth muscle tone by modulating intracellular sphingosine kinase mediated signalling. 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 smooth muscle tone, in particular aberrant, unwanted or otherwise inappropriate vascular, bronchial or intestinal smooth muscle tone.

Abstract: The present invention relates generally to a method of modulating endothelial cell functional characteristics and to agents useful for same. More particularly, the present invention relates to a method of modulating vascular endothelial cell pro-inflammatory and angiogenic phenotypes by modulating the functional levels of intracellular sphingosine kinase. The method of the present invention is useful, inter alia, in relation to the treatment and/or prophylaxis of conditions which are characterised by inadequate endothelial cell functioning and may include conditions such as vascular engraftment, organ transplantation or wound healing or conditions which are characterised by an aberrant endothelial cell inflammatory or angiogenic phenotype. Further, the method of the present invention facilitates the development of agents, such as functionally manipulated endothelial cell populations, for a range of therapeutic and/or prophylactic uses.

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.

Abstract: The present invention relates generally to a method of modulating cellular activity and agents useful for same. More particularly, the present invention contemplates a method of modulating endothelial cell activity and even more particularly endothelial cell adhesion molecule expression. Most particularly, the present invention provides a method of treating coronary heart disease by preventing or reducing endothelial cell adhesion molecule expression.

Abstract: A screening method for identifying a therapeutic candidate for a coronary heart disease or an inflammatory condition is disclosed. The screening method tests for the presence or absence of an effect by a putative therapeutic agent on a component of a sphingosine kinase signaling pathway.

Abstract: The present invention relates generally to a method of modulating cellular activity and agents useful for same. More particularly, the present invention contemplates a method of modulating endothelial cell activity and even more particularly endothelial cell adhesion molecule expression. Most particularly, the present invention provides a method of treating coronary heart disease by preventing or reducing endothelial cell adhesion molecule expression.