Molecular structure and function of angiotensin type 2 receptor.
More than two isoforms have been identified for angiotensin receptors based on their ligand selectivity. The objective of this study is to determine the molecular structure of angiotensin type 2 receptor (AT2), whose physiological functions are still an enigma despite extensive studies on its distribution in fetal tissues. We expression-cloned a cDNA of an affinity-purified AT2 from rat pheochromocytoma cells (PC12w). The AT2 cDNA clone comprises 2,868 nucleotides and encodes a 363 amino acid protein with seven putative transmembrane domains. The dissociation constant for its binding to 125I-CGP42112A, an AT2-specific ligand, was 0.11 +/- 0.01 nM. Its binding to 0.5 nM 125I-[Sar1,Ile8]-Ang II was not inhibited by Dup 753 but by PD123319 (IC50 = 1.7 +/- 0.2 nM). These binding features are characteristic of angiotensin type 2 receptor. The amino acid sequence analysis of the purified AT2 corroborated the amino terminus of the deduced primary structure of AT2. Angiotensin type 1 receptor (AT1) is the most closely related to AT2 but with only 32% amino acid sequence identity. Angiotensin II attenuated membrane-associated protein tyrosine phosphatase activity in the COS-7 cells stably expressing AT2 through a pertussis toxin-sensitive G protein. However, the physiological function of AT2 in the fetal kidney is still unresolved.
Kambayashi
Y
Y
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee.
Takahashi
K
K
Bardhan
S
S
Inagami
T
T
D000595:Amino Acid Sequence; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D007668:Kidney / Q000502:physiology; D007700:Kinetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000235:genetics* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014162:Transfection
D057911:Angiotensin Receptor Antagonists; D018076:DNA, Complementary; D011945:Receptors, Angiotensin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases