Identification and functional characterization of novel phosphorylation sites in TAK1-Binding Protein (TAB) 1
Wolf, Alexander ;
Beuerlein, Knut ;
Eckart, Christoph ;
Weiser, Hendrik ;
Dickkopf, Beate ;
Müller, Helmut ;
Sakurai, Hiroaki ;
Kracht, Michael
Originalveröffentlichung:
(2011) PLoS ONE, 6(12): e29256; doi:10.1371/journal.pone.0029256
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URN: urn:nbn:de:hebis:26-opus-85370
URL: http://geb.uni-giessen.de/geb/volltexte/2012/8537/
Freie Schlagwörter (Englisch):
TAK1-Binding Protein (TAB) 1 , phosphorylation sites , p38 MAPK activity , immune response , cellular signal transduction
Sammlung:
Open Access - Publikationsfonds
Universität
Justus-Liebig-Universität Gießen
Institut:
Rudolf-Buchheim-Institute of Pharmacology
Fachgebiet:
Medizin
DDC-Sachgruppe:
Medizin
Dokumentart:
Aufsatz
Sprache:
Englisch
Erstellungsjahr:
2011
Publikationsdatum:
04.01.2012
Kurzfassung auf Englisch:
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.
Lizenz:
Creative Commons - Namensnennung
