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@ARTICLE{Niehrs:292456,
      author       = {C. Niehrs$^*$ and C. Seidl$^*$ and H. Lee$^*$},
      title        = {{A}n '{R}-spondin code' for multimodal signaling {ON}-{OFF}
                      states.},
      journal      = {Bioessays},
      volume       = {46},
      number       = {10},
      issn         = {0265-9247},
      address      = {New York, NY},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2024-01723},
      pages        = {e2400144},
      year         = {2024},
      note         = {#EA:A050#LA:A050# / DKFZ-ZMBH Alliance / 2024
                      Oct;46(10):e2400144},
      abstract     = {R-spondins (RSPOs) are a family of secreted proteins and
                      stem cell growth factors that are potent co-activators of
                      Wnt signaling. Recently, RSPO2 and RSPO3 were shown to be
                      multifunctional, not only amplifying Wnt- but also binding
                      BMP- and FGF receptors to downregulate signaling. The common
                      mechanism underlying these diverse functions is that RSPO2
                      and RSPO3 act as 'endocytosers' that link transmembrane
                      proteins to ZNRF3/RNF43 E3 ligases and trigger target
                      internalization. Thus, RSPOs are natural protein targeting
                      chimeras for cell surface proteins. Conducting data mining
                      and cell surface binding assays we report additional
                      candidate RSPO targets, including SMO, PTC1,2, LGI1, ROBO4,
                      and PTPR(F/S). We propose that there is an 'R-spondin code'
                      that imparts combinatorial signaling ON-OFF states of
                      multiple growth factors. This code involves the modular RSPO
                      domains, notably distinct motifs in the divergent RSPO-TSP1
                      domains to mediate target interaction and internalization.
                      The RSPO code offers a novel framework for the understanding
                      how diverse signaling pathways may be coordinately regulated
                      in development and disease.},
      subtyp        = {Review Article},
      keywords     = {BMP (Other) / FGF (Other) / Hedgehog (Other) / R‐spondin
                      (Other) / Wnt (Other) / axon guidance (Other) / phosphatases
                      (Other) / receptor internalization (Other)},
      cin          = {A050},
      ddc          = {540},
      cid          = {I:(DE-He78)A050-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39180250},
      doi          = {10.1002/bies.202400144},
      url          = {https://inrepo02.dkfz.de/record/292456},
}