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https://hdl.handle.net/2440/52363
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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-α-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 |
DOI: | 10.1074/jbc.M804658200 |
Published version: | http://dx.doi.org/10.1074/jbc.m804658200 |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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