Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation.

ABSTRACT: Sphingosine kinase 1 is an agonist-activated signalling enzyme that catalyses the formation of sphingosine 1-phosphate, a lipid second messenger that has been implicated in a number of agonist-driven cellular responses, including stimulation of cell proliferation, inhibition of apoptosis and expression of inflammatory molecules. Although agonist-induced stimulation of sphingosine kinase activity is critical in a number of signalling pathways, nothing has been known of the molecular mechanism of this activation. Here we show that this activation results directly from phosphorylation of sphingosine kinase 1 at Ser225, and present several lines of evidence to show compellingly that the activating kinase is ERK1/2 or a close relative. Furthermore, we show that phosphorylation of sphingosine ki

SUBMITTER: Pitson SM 

PROVIDER: S-EPMC213794 | biostudies-literature | 2003 Oct

REPOSITORIES: biostudies-literature