High impact information on Sphk2

• Here, we report on the generation of sphingosine kinase 2 (SPHK2) knockout mice and demonstrate that this enzyme is essential for FTY720 phosphate formation in vivo [1].
• Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720 [2].
• We generated sphingosine kinase 2 (SPHK2) null mice to demonstrate that this kinase is responsible for FTY720 phosphorylation and thereby its subsequent actions on the immune system [2].
• We now report the metabolic activation of FTY720 by sphingosine kinase-2 and potent activation of vascular endothelial cell functions in vitro and in vivo by phosphorylated FTY720 (FTY720-P) [3].
• To investigate the distribution of all three SK channel subunits in the mouse central nervous system, we performed immunohistochemistry using sequence-specific antibodies directed against SK1, SK2, and SK3 proteins [4].

Anatomical context of Sphk2

• Expression of SK1 and SK2 proteins revealed a partly overlapping distribution pattern restricted to a limited number of brain areas (e.g., neocortex, hippocampal formation) [4].

Associations of Sphk2 with chemical compounds

• SK activity was measured by an in vitro kinase assay using sphingosine as substrate.Key results:Nucleotide stimulation caused biphasic activation of SK-1, but not SK-2 [5].

Regulatory relationships of Sphk2

• Such findings appear to reflect a requirement for Sphk2 to suppress IL-2 signaling because, in Sphk2(-/-) CD4(+) T cells, IL-2 induced abnormally accentuated STAT5 phosphorylation and small interfering RNA knockdown of STAT5 abrogated their hyperactive phenotype [6].

References