Identification and Functional Characterization of Novel Phosphorylation Sites in TAK1-binding Protein (TAB) 1

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jan 5

PMID 22216226

Citations 11

Authors

Alexander Wolf

Knut Beuerlein

Christoph Eckart

Hendrik Weiser

Beate Dickkopf

Helmut Muller

Hiroaki Sakurai

Michael Kracht

Affiliations

Soon will be listed here.

Abstract

TAB1 was defined as a regulatory subunit of the protein kinase TAK1, which functions upstream in the pathways activated by interleukin (IL)-1, tumor necrosis factor (TNF), toll-like receptors (TLRs) and stressors. However, TAB1 also functions in the p38 MAPK pathway downstream of TAK1. We identified amino acids (aa) 452/453 and 456/457 of TAB1 as novel sites phosphorylated by TAK1 as well as by p38 MAPK in intact cells as well as in vitro. Serines 452/453 and 456/457 were phosphorylated upon phosphatase blockade by calyculin A, or in response to IL-1 or translational stressors such as anisomycin and sorbitol. Deletion or phospho-mimetic mutations of aa 452-457 of TAB1 retain TAB1 and p38 MAPK in the cytoplasm. The TAB1 mutant lacking aa 452-457 decreases TAB1-dependent phosphorylation of p38 MAPK. It also enhances TAB1-dependent CCL5 secretion in response to IL-1 and increases activity of a post-transcriptional reporter gene, which contains the CCL5 3' untranslated region. These data suggest a complex role of aa 452-457 of TAB1 in controlling p38 MAPK activity and subcellular localization and implicate these residues in TAK1- or p38 MAPK-dependent post-transcriptional control of gene expression.

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