Relationship between ligand binding and YIPP motif in the C-terminal region of human AT_1 receptor

摘要

The YIPP (tyrosine-isoleucine-proline-proline, amino acids 319-322) motif within the C-terminal part of the human AT_1 receptor is associated with angiotensin II (AII)-induced activation of the Jak-STAT pathway and phospholipase Cγ1 phosphorylation. We report here that mutations of the YIPP motif strongly affect ligand-binding to the receptor. We analysed AT_1 receptors of the wild type (WT) and ll mutants with a FLAG-epitope-tag within their C-terminal portion. Mutations of the "P-P" amino acid sequence of this motif decreased both AII binding and the AII-induced intracellular Ca~(2+) transients. Mutant and WT receptors were expressed equally in the cell membrane and were localized within the plasma membrane. These results suggest that the "P-P" amino acid sequence within the YIPP motif is important for AII binding to the AT_1 receptor.