GPCR activation of CFTR through two independent phosphorylation pathways

• DOI: 10.1096/fasebj.27.1_supplement.1148.17
• Publication Date: 2021-06-16T10:12:44Z
• Authors: Arnaud Billet; John William Hanr...
• Keywords: 0301 basic medicine; 03 medical and health sciences

Cystic Fibrosis Transmembrane conductance Regulator (CFTR) activation by PKA and PKC has been extensively studied, however its regulation receptors is less well understood. To study signaling upstream of the kinases, we measured whole‐cell Cl‐currents in BHK cells cotransfected with GPCRs CFTR. In expressing M3 muscarinic acetylcholine receptor, agonist carbachol (Cch) caused strong CFTR through two pathways; canonical PKA‐dependent mechanism a second that involves tyrosine phosphorylation. The role was suggested partial mutant lacking residues mediate stimulation kinase c‐Src. kinases ability Cch to stimulate 15SA CFTR, which lacks 15 potential sites unresponsive stimulation, also sensitivity response inhibitors results suggest phosphorylation both contribute are expressed at apical membrane intestinal airway epithelia. Supported GEPROM, GRASP, McGill (CIHR) Chemical Biology program, Canadian Foundation for Innovation.