Phosphorylation/dephosphorylation of human SULT4A1: Role of Erk1 and PP2A

Mitchell, Deanne J., Butcher, Neville J. and Minchin, Rodney F. (2011) Phosphorylation/dephosphorylation of human SULT4A1: Role of Erk1 and PP2A. Biochimica et Biophysica Acta - Molecular Cell Research, 1813 1: 231-237. doi:10.1016/j.bbamcr.2010.09.011

Author Mitchell, Deanne J.
Butcher, Neville J.
Minchin, Rodney F.
Title Phosphorylation/dephosphorylation of human SULT4A1: Role of Erk1 and PP2A
Journal name Biochimica et Biophysica Acta - Molecular Cell Research   Check publisher's open access policy
ISSN 0167-4889
Publication date 2011-01
Year available 2010
Sub-type Article (original research)
DOI 10.1016/j.bbamcr.2010.09.011
Volume 1813
Issue 1
Start page 231
End page 237
Total pages 7
Editor Anita Corbett
N. Pfanner
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Collection year 2011
Language eng
Formatted abstract
SULT4A1 is a cytosolic sulfotransferase that shares little homology with other human sulfotransferases but is highly conserved between species. It is found in neurons located in several regions of the brain. Recently, the stability of SULT4A1 was shown to be regulated by Pin1, a peptidyl-prolyl cis-trans isomerase implicated in several neurodegenerative diseases. Since Pin1 binds preferentially to phosphoproteins, these findings suggested that SULT4A1 is post-translationally modified. In this study, we show that the Thr11 residue of SULT4A1, which is involved in Pin1 binding is phosphorylated. MEK inhibition was shown to abolish Pin1 mediated degradation of SULT4A1 while in vitro phosphorylation assays using alanine substitution mutants of SULT4A1 demonstrated phosphorylation of Thr11 by ERK1. We also show that dephosphorylation was catalyzed by the protein phosphatase 2A. The PP2A regulatory subunit, Bβ was identified from a yeast-2-hybrid screen of human brain cDNA as a SULT4A1 interacting protein. This was further confirmed by GST pull-downs and immunoprecipitation. Other members of the B subunit (α δ γ) did not interact with SULT4A1. Taken together, these studies indicate that SULT4A1 stability is regulated by post-translational modification that involves the ERK pathway and PP2A. The phosphorylation of SULT4A1 allows interaction with Pin1, which then promotes degradation of the sulfotransferase.

Research Highlights: ►ERK1 phosphorylates SULT4A1. ►Dephosphorylation of ser/thr residues on SULT4A1 is mediated by PP2A. ►SULT4A1 stability is regulated by post-translational modifications involving ERK1 and PP2A.
© 2010 Elsevier B.V. All rights reserved.
Keyword Sulfotransferase
Protein phosphatase 2A
Isomerase Pin1
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 12 October 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 22 Mar 2011, 11:25:51 EST by Bacsweet Kaur on behalf of School of Biomedical Sciences