ArticleThe Journal of biological chemistry2012
A dual role for receptor-interacting protein kinase 2 (RIP2) kinase activity in nucleotide-binding oligomerization domain 2 (NOD2)-dependent autophagy.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 89 citations in OpenAlex.
- Arsenic disrupts autophagosome-lysosome fusion in a zinc dependent manner across multiple human skin and lung cells lines.Archives of toxicology · 2026Article
- RNA stability: a novel perspective on gene regulatory networks in bovine mastitis.BMC genomics · 2025Article
- Resolving the field: a role for Nod2 in T cells.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
- Gadd45B Deficiency Drives Radio-Resistance in BRAFCancers · 2025Article
- Role and molecular mechanism of NOD2 in chronic non-communicable diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- MAP3K4 kinase action and dual role in cancer.Discover oncology · 2024Review
- Analysis of alternative splicing in chicken macrophages transfected with overexpression/knockdown ofAnimal biotechnology · 2023Article
- NOD2 inhibits the proliferation of esophageal adenocarcinoma cells through autophagy.Journal of cancer research and clinical oncology · 2023Article
- Multifaceted roles and regulation of nucleotide-binding oligomerization domain containing proteins.Frontiers in immunology · 2023Review
- Article
- Regulation of Immune Homeostasis via Muramyl Peptides-Low Molecular Weight Bioregulators of Bacterial Origin.Microorganisms · 2022Review
- Gene expression profiling of RIP2-knockdown in HD11 macrophages - elucidation of potential pathways (gene network) when challenged with avian pathogenic E.coli (APEC).BMC genomics · 2022Article
- Essential Role of the Innate Immune Adaptor RIP2 in the Response to Otitis Media.Frontiers in genetics · 2022Article
- Harnessing the Complete Repertoire of Conventional Dendritic Cell Functions for Cancer Immunotherapy.Pharmaceutics · 2020Review
- Autophagy and microbial pathogenesis.Cell death and differentiation · 2020Review
- Innate immune receptor NOD2 mediates LGR5Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Thinking Outside the Box: Innate- and B Cell-Memory Responses as Novel Protective Mechanisms Against Tuberculosis.Frontiers in immunology · 2020Review
- XIAP controls RIPK2 signaling by preventing its deposition in speck-like structures.Life science alliance · 2019Article
- Loss of myeloid-specific protein phosphatase 2A enhances lung injury and fibrosis and results in IL-10-dependent sensitization of epithelial cell apoptosis.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- NOD-like receptors: major players (and targets) in the interface between innate immunity and cancer.Bioscience reports · 2019Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Autophagy is triggered by the intracellular bacterial sensor NOD2 (nucleotide-binding, oligomerization domain 2) as an anti-bacterial response. Defects in autophagy have been implicated in Crohn's disease susceptibility. The molecular mechanisms of activation and regulation of this process by NOD2 are not well understood, with recent studies reporting conflicting requirements for RIP2 (receptor-interacting protein kinase 2) in autophagy induction. We examined the requirement of NOD2 signaling mediated by RIP2 for anti-bacterial autophagy induction and clearance of Salmonella typhimurium in the intestinal epithelial cell line HCT116. Our data demonstrate that NOD2 stimulates autophagy in a process dependent on RIP2 tyrosine kinase activity. Autophagy induction requires the activity of the mitogen-activated protein kinases MEKK4 and p38 but is independent of NFκB signaling. Activation of autophagy was inhibited by a PP2A phosphatase complex, which interacts with both NOD2 and RIP2. PP2A phosphatase activity inhibited NOD2-dependent autophagy but not activation of NFκB or p38. Upon stimulation of NOD2, the phosphatase activity of the PP2A complex is inhibited through tyrosine phosphorylation of the catalytic subunit in a process dependent on RIP2 activity. These findings demonstrate that RIP2 tyrosine kinase activity is not only required for NOD2-dependent autophagy but plays a dual role in this process. RIP2 both sends a positive autophagy signal through activation of p38 MAPK and relieves repression of autophagy mediated by the phosphatase PP2A.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.