The C-terminal of the α1b-adreneroceptor is a key determinant for its structure integrity and biological functions

ABSTRACT The C-terminal of G protein-coupled receptors is now recognized as being important for protein activation and signaling function. To detect the role tail in receptor activation, we used α1b-AR, which has a long 164 amino acids. We constructed intramolecular FRET sensors, was truncated to 10 (∆C-10), 20 (∆C-20), 30 (∆C-30), 50 (∆C-50), 70 (∆C-70), or 90 (∆C-90). mutants ∆C-10, ∆C-20, ∆C-30 cannot induce signal changes downstream ERK1/2 phosphorylation. However, ∆C-50, ∆C-70, ∆C-90 significant phosphorylation, especially ∆C-90. This particularly true case ∆C-90, ∆C-50 retained potential phosphorylation sites (Ser401, Ser404, Ser408, Ser410). showed an increase agonist-induced PKC- endocytosis-dependent EGFR-, src-, β-arrestin2-independent.