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@ARTICLE{Bonus:874892,
      author       = {Bonus, Michele and Sommerfeld, Annika and Qvartskhava,
                      Natalia and Görg, Boris and Ludwig, Beatrice Stefanie and
                      Kessler, Horst and Gohlke, Holger and Häussinger, Dieter},
      title        = {{E}vidence for functional selectivity in {TUDC}- and
                      nor{UDCA}-induced signal transduction via α5β1 integrin
                      towards choleresis},
      journal      = {Scientific reports},
      volume       = {10},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {FZJ-2020-01684},
      pages        = {5795},
      year         = {2020},
      abstract     = {Functional selectivity is the ligand-specific activation of
                      certain signal transduction pathways at a receptor and has
                      been described for G protein-coupled receptors. However, it
                      has not yet been described for ligands interacting with
                      integrins without αI domain. Here, we show by molecular
                      dynamics simulations that four side chain-modified
                      derivatives of tauroursodeoxycholic acid (TUDC), an agonist
                      of α5β1 integrin, differentially shift the conformational
                      equilibrium of α5β1 integrin towards the active state, in
                      line with the extent of β1 integrin activation from
                      immunostaining. Unlike TUDC, 24-nor-ursodeoxycholic acid
                      (norUDCA)-induced β1 integrin activation triggered only
                      transient activation of extracellular signal-regulated
                      kinases and p38 mitogen-activated protein kinase and,
                      consequently, only transient insertion of the bile acid
                      transporter Bsep into the canalicular membrane, and did not
                      involve activation of epidermal growth factor receptor.
                      These results provide evidence that TUDC and norUDCA exert a
                      functional selectivity at α5β1 integrin and may provide a
                      rationale for differential therapeutic use of UDCA and
                      norUDCA.},
      cin          = {NIC / JSC / IBI-7},
      ddc          = {600},
      cid          = {I:(DE-Juel1)NIC-20090406 / I:(DE-Juel1)JSC-20090406 /
                      I:(DE-Juel1)IBI-7-20200312},
      pnm          = {511 - Computational Science and Mathematical Methods
                      (POF3-511) / Forschergruppe Gohlke $(hkf7_20170501)$},
      pid          = {G:(DE-HGF)POF3-511 / $G:(DE-Juel1)hkf7_20170501$},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32242141},
      UT           = {WOS:000540497600002},
      doi          = {10.1038/s41598-020-62326-y},
      url          = {https://juser.fz-juelich.de/record/874892},
}