Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/52363
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Deactivation of Sphingosine Kinase 1 by Protein Phosphatase 2A
Author: Barr, R.
Lynn, H.
Moretti, P.
Khew-Goodall, Y.
Pitson, S.
Citation: Journal of Biological Chemistry, 2008; 283(50):34994-35002
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2008
ISSN: 0021-9258
1083-351X
Statement of
Responsibility: 
Renae K. Barr, Helen E. Lynn, Paul A. B. Moretti, Yeesim Khew-Goodall, and Stuart M. Pitson
Abstract: Sphingosine kinase 1 (SK1) is an important regulator of cellular signaling that has been implicated in a broad range of cellular processes. Cell exposure to a wide array of growth factors, cytokines, and other cell agonists can result in a rapid and transient increase in SK activity via an activating phosphorylation. We have previously identified extracellular signal-regulated kinases 1 and 2 (ERK1/2) as the kinases responsible for the phosphorylation of human SK1 at Ser225, but the corresponding phosphatase targeting this phosphorylation has remained undefined. Here, we provide data to support a role for protein phosphatase 2A (PP2A) in the deactivation of SK1 through dephosphorylation of phospho-Ser225. The catalytic subunit of PP2A (PP2Ac) was found to interact with SK1 using both GST-pulldown and coimmunoprecipitation analyses. Coexpression of PP2Ac with SK1 resulted in reduced Ser225 phosphorylation of SK1 in human embryonic kidney (HEK293) cells. In vitro phosphatase assays showed that PP2Ac dephosphorylated both recombinant SK1 and a phosphopeptide based on the phospho-Ser225 region of SK1. Finally, both basal and tumor necrosis factor-╬▒-stimulated cellular SK1 activity were regulated by molecular manipulation of PP2Ac activity. Thus, PP2A appears to function as an endogenous regulator of SK1 phosphorylation.
Keywords: Muscle, Skeletal; Subcellular Fractions; Animals; Rabbits; Humans; Glutathione Transferase; Phosphotransferases (Alcohol Group Acceptor); Extracellular Signal-Regulated MAP Kinases; Serine; Tumor Necrosis Factor-alpha; Gene Silencing; Enzyme Activation; Protein Structure, Tertiary; Phosphorylation; Protein Phosphatase 2
RMID: 0020084092
DOI: 10.1074/jbc.M804658200
Appears in Collections:Molecular and Biomedical Science 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.