p38(MAPK)/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection
Standard
p38(MAPK)/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection. / 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.
In: NAT CELL BIOL, Vol. 19, No. 10, 10.2017, p. 1248-1259.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - p38(MAPK)/MK2-dependent phosphorylation controls cytotoxic RIPK1 signalling in inflammation and infection
AU - Menon, Manoj B
AU - Gropengießer, Julia
AU - Fischer, Jessica
AU - Novikova, Lena
AU - Deuretzbacher, Anne
AU - Lafera, Juri
AU - Schimmeck, Hanna
AU - Czymmeck, Nicole
AU - Ronkina, Natalia
AU - Kotlyarov, Alexey
AU - Aepfelbacher, Martin
AU - Gaestel, Matthias
AU - Ruckdeschel, Klaus
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
KW - Animals
KW - Apoptosis
KW - Bacterial Proteins
KW - Cytosol
KW - Female
KW - Genotype
KW - HEK293 Cells
KW - Host-Pathogen Interactions
KW - Humans
KW - I-kappa B Kinase
KW - Inflammation
KW - Intracellular Signaling Peptides and Proteins
KW - MAP Kinase Kinase Kinases
KW - Macrophages
KW - Male
KW - Membrane Proteins
KW - Mice, Knockout
KW - Necrosis
KW - Phenotype
KW - Phosphorylation
KW - Protein-Serine-Threonine Kinases
KW - Receptor-Interacting Protein Serine-Threonine Kinases
KW - Receptors, Tumor Necrosis Factor, Type I
KW - Serine
KW - Signal Transduction
KW - Time Factors
KW - Transfection
KW - Tumor Necrosis Factor-alpha
KW - Yersinia Infections
KW - Yersinia enterocolitica
KW - p38 Mitogen-Activated Protein Kinases
KW - Journal Article
U2 - 10.1038/ncb3614
DO - 10.1038/ncb3614
M3 - SCORING: Journal article
C2 - 28920954
VL - 19
SP - 1248
EP - 1259
JO - NAT CELL BIOL
JF - NAT CELL BIOL
SN - 1465-7392
IS - 10
ER -