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@ARTICLE{Kamiyama:167440,
      author       = {M. Kamiyama$^*$ and H. Augustin$^*$},
      title        = {{A}lternatively {S}pliced {F}orm of {A}ngiopoietin-2 as a
                      {N}ew {V}ascular {R}heostat.},
      journal      = {Cancer research},
      volume       = {81},
      number       = {1},
      issn         = {0008-5472},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2021-00344},
      pages        = {35-37},
      year         = {2021},
      note         = {DKFZ-ZMBH Alliance#EA:A190#LA:A190#},
      abstract     = {Angiopoietin (ANPGT)-TIE signaling serves as a critical
                      regulator of vessel maturation controlling vascular
                      quiescence, maintenance, and homeostasis (primarily through
                      ANGPT1-TIE2 signaling), as well as enabling vascular
                      plasticity and responsiveness to exogenous cytokines
                      (primarily through antagonistically acting ANGPT2). An
                      alternatively spliced form of ANGPT2 (ANGPT2443) was first
                      reported 20 years ago. Yet, little is known to this day
                      about its biological functions. In this issue of Cancer
                      Research, Kapiainen and colleagues report an elegant series
                      of experiments adding to the complexity and contextuality of
                      ANGPT-TIE signaling. The authors studied the function of
                      ANGPT2443 in cellular experiments as well as in a genetic
                      model in vivo, revealing that it is proteolytically cleaved
                      into a lower molecular weight isoform (termed ANGPT2DAP)
                      that lacks the superclustering domain necessary for multimer
                      formation. When compared with full-length ANGPT2, ANGPT2443
                      and ANGPT2DAP showed lower binding affinity to α5β1
                      integrin, but were more potent inhibitors of ANGPT1-TIE2
                      signaling. Functionally, ANGPT2443 impaired vessel
                      enlargement and vein morphogenesis during postnatal retinal
                      angiogenesis. Tumor experiments in Angpt2443-expressing mice
                      showed enhanced destabilization of the lung vasculature,
                      with varying effects on metastasis. Taken together, the
                      study provides important insight into the significance of
                      ANGPT2 alternative splicing and identifies ANGPT2443 and
                      ANGPT2DAP as a biological rheostat of ANGPT1-TIE2 signaling.
                      Future work will need to characterize the relative ratios
                      and functional contributions of the ANGPT2 variants in
                      different pathophysiologic settings.See related article by
                      Kapiainen et al., p. 129.},
      subtyp        = {Letter},
      cin          = {A190},
      ddc          = {610},
      cid          = {I:(DE-He78)A190-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33571136},
      doi          = {10.1158/0008-5472.CAN-20-3695},
      url          = {https://inrepo02.dkfz.de/record/167440},
}