Relationship between ligand binding and YIPP motif in the C-terminal region of human AT1 receptor.
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 Cgamma1 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 11 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.
Inada
Yoichi
Y
Department of Pharmacology, Shinshu University School of Medicine, 3-1-1 Asahi, 390-8621, Matsumoto, Japan.
Nakane
Tokio
T
Chiba
Shigetoshi
S
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011392:Proline / Q000737:chemistry; D011869:Radioligand Assay; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D007457:Iodine Radioisotopes; D008024:Ligands; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D011392:Proline; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium