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Updated: Sep 30, 2026

Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
Published on: March 9, 2015
Genistein modifies the activation kinetics and magnitude of phosphorylated wild-type and G551D-CFTR chloride currents
L Bulteau-Pignoux1, R Dérand, T Métayé
1UMR CNRS 6558, LBSC, Université de Poitiers, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France.
Abstract:
We have studied the mechanism by which genistein activates cystic fibrosis transmembrane conductance regulator (CFTR) in CHO cells expressing wild type or G551D-CFTR. In wild-type CHO cells, after exposure to 2.5 microM forskolin, 25 microM genistein induced a further 2-fold and rapid increase of the forskolin-activated CFTR current. In both types of cells, when forskolin was added after genistein preincubation, whole-cell current density was greatly reduced compared to that measured when genistein was added after phosphorylation of CFTR, and all activation kinetic parameters were significantly altered. Genistein had no effect on the adenylate cyclase activity. Our results suggest that the occupancy of a putative genistein binding site is critical for the gating mechanism of CFTR chloride channels, which, depending on the phosphorylation status of the R-domain, drives CFTR either into a refractory state or alternatively to a highly activated state.
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