Renal mesangial cells: moving on sphingosine kinase-1.

Sphingosine kinase-1 (SphK1) catalyses the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P), which acts on at least five specific G-protein-coupled receptors and also intracellularly. SphK1 has been implicated in cell proliferation, cancer growth, chemoresistance, immune cell functions and cell migration. In this issue of the British Journal of Pharmacology, Klawitter et al. demonstrate that extracellular nucleotides stimulate the migration of renal mesangial cells. The nucleotides furthermore upregulated SphK1 expression and activity, and this enzyme was required for nucleotide-induced migration. Together with previous findings, these data raise exciting questions: by which mechanism does SphK1 regulate migration in mesangial cells, how is the interplay of purinoceptors and S1P receptors organized in these cells, and how would SphK1-deficient mice respond to kidney damage?