Evidence for functional selectivity in TUDC- and norUDCA-induced signal transduction via α₅β₁ integrin towards choleresis.

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-regula

SUBMITTER: Bonus M 

PROVIDER: S-EPMC7118123 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature