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https://hdl.handle.net/2440/9425
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Type: | Journal article |
Title: | Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation |
Author: | Pitson, S. Moretti, P. Zebol, J. Lynn, H. Xia, P. Vadas, M. Wattenberg, B. |
Citation: | The EMBO Journal, 2003; 22(20):5491-5500 |
Publisher: | Nature Publishing Group |
Issue Date: | 2003 |
ISSN: | 0261-4189 1460-2075 |
Statement of Responsibility: | Stuart M. Pitson, Paul A. B. Moretti, Julia R. Zebol, Helen E. Lynn, Pu Xia, Mathew A. Vadas and Binks W. Wattenberg |
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 kinase 1 at Ser225 results not only in an increase in enzyme activity, but is also necessary for translocation of the enzyme from the cytosol to the plasma membrane. Thus, these studies have elucidated the mechanism of agonist-mediated sphingosine kinase activation, and represent a key finding in understanding the regulation of sphingosine kinase/sphingosine 1-phosphate-controlled signalling pathways. |
Keywords: | Cell Line Animals Humans Phosphotransferases (Alcohol Group Acceptor) Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Recombinant Proteins DNA Primers Microscopy, Confocal Transfection Amino Acid Substitution Mutagenesis, Site-Directed Sequence Alignment Enzyme Activation Amino Acid Sequence Base Sequence Phosphorylation Kinetics Point Mutation |
Description: | Copyright © 2003 European Molecular Biology Organization |
DOI: | 10.1093/emboj/cdg540 |
Published version: | http://dx.doi.org/10.1093/emboj/cdg540 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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