Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/9544
Citations | ||
Scopus | Web of ScienceĀ® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-a signaling |
Author: | Xia, P. Wang, L. Moretti, P. Albanese, N. Chai, F. Pitson, S. D'Andrea, R. Gamble, J. Vadas, M. |
Citation: | Journal of Biological Chemistry, 2002; 277(10):7996-8003 |
Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
Issue Date: | 2002 |
ISSN: | 0021-9258 1083-351X |
Statement of Responsibility: | Pu Xia, Lijun Wang, Paul A. B. Moretti, Nathaniel Albanese, Fugui Chai, Stuart M. Pitson, Richard J. D'Andrea, Jennifer R. Gamble and Mathew A. Vadas |
Abstract: | Tumor necrosis factor-alpha (TNF) receptor-associated factor 2 (TRAF2) is one of the major mediators of TNF receptor superfamily transducing TNF signaling to various functional targets, including activation of NF-kappa B, JNK, and antiapoptosis. We investigated how TRAF2 mediates differentially the distinct downstream signals. We now report a novel mechanism of TRAF2-mediated signal transduction revealed by an association of TRAF2 with sphingosine kinase (SphK), a lipid kinase that is responsible for the production of sphingosine 1-phosphate. We identified a TRAF2-binding motif of SphK that mediated the interaction between TRAF2 and SphK resulting in the activation of the enzyme, which in turn is required for TRAF2-mediated activation of NF-kappa B but not JNK. In addition, by using a kinase inactive dominant-negative SphK and a mutant SphK that lacks TRAF2-binding motif we show that the interaction of TRAF2 with SphK and subsequent activation of SphK are critical for prevention of apoptosis during TNF stimulation. These findings show a role for SphK in the signal transduction by TRAF2 specifically leading to activation of NF-kappa B and antiapoptosis. |
Keywords: | Endothelium, Vascular Umbilical Veins Cells, Cultured Cell Line Humans Glutathione Transferase Phosphotransferases (Alcohol Group Acceptor) Tumor Necrosis Factor-alpha TNF Receptor-Associated Factor 2 Proteins NF-kappa B Recombinant Fusion Proteins DNA, Complementary Blotting, Western Precipitin Tests Mutagenesis, Site-Directed Signal Transduction Apoptosis Cell Survival Enzyme Activation Protein Binding Genes, Dominant Mutation Genes, Reporter Plasmids Models, Biological Time Factors |
DOI: | 10.1074/jbc.M111423200 |
Published version: | http://www.jbc.org/cgi/content/abstract/277/10/7996 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.