% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Stafford:165135,
      author       = {Stafford, Che A and Gassauer, Alicia-Marie and de Oliveira
                      Mann, Carina C and Tanzer, Maria C and Fessler, Evelyn and
                      Wefers, Benedikt and Nagl, Dennis and Kuut, Gunnar and
                      Sulek, Karolina and Vasilopoulou, Catherine and Schwojer,
                      Sophia J and Wiest, Andreas and Pfautsch, Marie K and Wurst,
                      Wolfgang and Yabal, Monica and Fröhlich, Thomas and Mann,
                      Matthias and Gisch, Nicolas and Jae, Lucas T and Hornung,
                      Veit},
      title        = {{P}hosphorylation of muramyl peptides by {NAGK} is required
                      for {NOD}2 activation.},
      journal      = {Nature},
      volume       = {609},
      number       = {7927},
      issn         = {0028-0836},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DZNE-2022-01440},
      pages        = {590 - 596},
      year         = {2022},
      note         = {CC BY: https://creativecommons.org/licenses/by/4.0/},
      abstract     = {Bacterial cell wall components provide various unique
                      molecular structures that are detected by pattern
                      recognition receptors (PRRs) of the innate immune system as
                      non-self. Most bacterial species form a cell wall that
                      consists of peptidoglycan (PGN), a polymeric structure
                      comprising alternating amino sugars that form strands
                      cross-linked by short peptides. Muramyl dipeptide (MDP) has
                      been well documented as a minimal immunogenic component of
                      peptidoglycan1-3. MDP is sensed by the cytosolic
                      nucleotide-binding oligomerization domain-containing protein
                      24 (NOD2). Upon engagement, it triggers pro-inflammatory
                      gene expression, and this functionality is of critical
                      importance in maintaining a healthy intestinal barrier
                      function5. Here, using a forward genetic screen to identify
                      factors required for MDP detection, we identified
                      N-acetylglucosamine kinase (NAGK) as being essential for the
                      immunostimulatory activity of MDP. NAGK is broadly expressed
                      in immune cells and has previously been described to
                      contribute to the hexosamine biosynthetic salvage pathway6.
                      Mechanistically, NAGK functions upstream of NOD2 by directly
                      phosphorylating the N-acetylmuramic acid moiety of MDP at
                      the hydroxyl group of its C6 position, yielding
                      6-O-phospho-MDP. NAGK-phosphorylated MDP-but not unmodified
                      MDP-constitutes an agonist for NOD2. Macrophages from mice
                      deficient in NAGK are completely deficient in MDP sensing.
                      These results reveal a link between amino sugar metabolism
                      and innate immunity to bacterial cell walls.},
      keywords     = {Acetylmuramyl-Alanyl-Isoglutamine: chemistry /
                      Acetylmuramyl-Alanyl-Isoglutamine: immunology /
                      Acetylmuramyl-Alanyl-Isoglutamine: metabolism /
                      Acetylmuramyl-Alanyl-Isoglutamine: pharmacology / Animals /
                      Bacteria: chemistry / Bacteria: immunology / Cell Wall:
                      chemistry / Hexosamines: biosynthesis / Immunity, Innate /
                      Macrophages: enzymology / Macrophages: immunology / Mice /
                      Nod2 Signaling Adaptor Protein: agonists / Nod2 Signaling
                      Adaptor Protein: metabolism / Peptidoglycan: chemistry /
                      Peptidoglycan: immunology / Phosphorylation /
                      Phosphotransferases (Alcohol Group Acceptor): deficiency /
                      Phosphotransferases (Alcohol Group Acceptor): genetics /
                      Phosphotransferases (Alcohol Group Acceptor): metabolism},
      cin          = {AG Wurst},
      ddc          = {500},
      cid          = {I:(DE-2719)1140001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9477735},
      pubmed       = {pmid:36002575},
      doi          = {10.1038/s41586-022-05125-x},
      url          = {https://pub.dzne.de/record/165135},
}