دورية
p38MAPK/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection
| العنوان: | p38MAPK/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection |
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| المؤلفون: | Menon, Manoj B., Gropengießer, Julia, Fischer, Jessica, Novikova, Lena, Deuretzbacher, Anne, Lafera, Juri, Schimmeck, Hanna, Czymmeck, Nicole, Ronkina, Natalia, Kotlyarov, Alexey, Aepfelbacher, Martin, Gaestel, Matthias, Ruckdeschel, Klaus |
| المصدر: | Nature Cell Biology; October 2017, Vol. 19 Issue: 10 p1248-1259, 12p |
| مستخلص: | Receptor-interacting protein kinase-1 (RIPK1), a master regulator of cell fate decisions, was identified as a direct substrate of MAPKAP kinase-2 (MK2) by phosphoproteomic screens using LPS-treated macrophages and stress-stimulated embryonic fibroblasts. p38MAPK/MK2 interact with RIPK1 in a cytoplasmic complex and MK2 phosphorylates mouse RIPK1 at Ser321/336 in response to pro-inflammatory stimuli, such as TNF and LPS, and infection with the pathogen Yersinia enterocolitica. MK2 phosphorylation inhibits RIPK1 autophosphorylation, curtails RIPK1 integration into cytoplasmic cytotoxic complexes, and suppresses RIPK1-dependent apoptosis and necroptosis. In Yersinia-infected macrophages, RIPK1 phosphorylation by MK2 protects against infection-induced apoptosis, a process targeted by Yersinia outer protein P (YopP). YopP suppresses p38MAPK/MK2 activation to increase Yersinia-driven apoptosis. Hence, MK2 phosphorylation of RIPK1 is a crucial checkpoint for cell fate in inflammation and infection that determines the outcome of bacteria–host cell interaction. |
| قاعدة البيانات: | Supplemental Index |
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Full Text Finder | تدمد: | 14657392 14764679 |
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| DOI: | 10.1038/ncb3614 |