Wolf, AlexanderAlexanderWolfBeuerlein, KnutKnutBeuerleinEckart, ChristophChristophEckartWeiser, HendrikHendrikWeiserDickkopf, BeateBeateDickkopfMüller, HelmutHelmutMüllerSakurai, HiroakiHiroakiSakuraiKracht, MichaelMichaelKracht2022-11-182012-01-042022-11-182011http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-85370https://jlupub.ub.uni-giessen.de/handle/jlupub/9622http://dx.doi.org/10.22029/jlupub-9010TAB1 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.enNamensnennung 3.0 InternationalTAK1-Binding Protein (TAB) 1phosphorylation sitesp38 MAPK activityimmune responsecellular signal transductionddc:610