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| Home > Publications database > Evidence for functional selectivity in TUDC- and norUDCA-induced signal transduction via α5β1 integrin towards choleresis > print |
| 001 | 874892 | ||
| 005 | 20210130004819.0 | ||
| 024 | 7 | _ | |a 10.1038/s41598-020-62326-y |2 doi |
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| 100 | 1 | _ | |a Bonus, Michele |0 0000-0003-4411-7342 |b 0 |
| 245 | _ | _ | |a Evidence for functional selectivity in TUDC- and norUDCA-induced signal transduction via α5β1 integrin towards choleresis |
| 260 | _ | _ | |a [London] |c 2020 |b Macmillan Publishers Limited, part of Springer Nature |
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| 520 | _ | _ | |a 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. |
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| 700 | 1 | _ | |a Görg, Boris |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Ludwig, Beatrice Stefanie |0 0000-0002-9420-931X |b 4 |
| 700 | 1 | _ | |a Kessler, Horst |0 0000-0002-7292-9789 |b 5 |
| 700 | 1 | _ | |a Gohlke, Holger |0 P:(DE-Juel1)172663 |b 6 |e Corresponding author |
| 700 | 1 | _ | |a Häussinger, Dieter |0 P:(DE-HGF)0 |b 7 |e Corresponding author |
| 773 | _ | _ | |a 10.1038/s41598-020-62326-y |g Vol. 10, no. 1, p. 5795 |0 PERI:(DE-600)2615211-3 |n 1 |p 5795 |t Scientific reports |v 10 |y 2020 |x 2045-2322 |
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