Role of C-terminal cytoplasmic domain of the AT2 receptor in ligand binding and signaling.
A stop codon at position 322 was introduced to generate a truncated, C-terminal-deleted AT2 receptor. Expression studies in Xenopus oocytes showed that C-terminal-deleted AT2 had reduced affinity to [(125)I]angiotensin II (K(d)=1.7 nM) and enhanced binding of the AT2-specific peptidic ligand [(125)I]CGP42112A (K(d)=0.097 nM). AT2 activation by angiotensin II resulted in reduction of cGMP levels in oocytes and this reduction was further enhanced by C-terminal deletion, implying that the C-terminus may have a negative effect on the AT2-mediated cGMP reduction. Moreover, interaction of the AT2 with the ATP-binding domain of the human ErbB3 receptor in yeast two-hybrid assay was abolished by C-terminal deletion. In summary, the C-terminal cytoplasmic tail of AT2 modulates its ligand binding and signaling properties.
Department of Biological Sciences, Bowling Green State University, Bowling Green, OH 43403, USA. pulakat@bgnet.bgsu.edu
Lakshmidevi
L
Pulakat
Amanda
A
Gray
Janean
J
Johnson
Dieter
D
Knowle
Veronica
V
Burns
Nara
N
Gavini
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D018388:Codon, Terminator; D006152:Cyclic GMP / Q000378:metabolism; D017931:DNA Primers; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D011945:Receptors, Angiotensin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014981:Xenopus
D018388:Codon, Terminator; D017931:DNA Primers; D008024:Ligands; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D006152:Cyclic GMP