RT Journal Article
SR Electronic
T1 Homologous and Heterologous Phosphorylation of the AT<sub>2</sub> Angiotensin Receptor by Protein Kinase C
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1156
OP 1161
DO 10.1124/mol.58.5.1156
VO 58
IS 5
A1 Olivares-Reyes, Jesus A.
A1 Jayadev, Suman
A1 Hunyady, László
A1 Catt, Kevin J.
A1 Smith, Roger D.
YR 2000
UL http://molpharm.aspetjournals.org/content/58/5/1156.abstract
AB The angiotensin AT2 receptor is an atypical seven transmembrane domain receptor that is coupled to activation of tyrosine phosphatase and inhibition of MAP kinase, and does not undergo agonist-induced internalization. An investigation of the occurrence and nature of AT2 receptor phosphorylation revealed that phorbol ester-induced activation of protein kinase C (PKC) in HA-AT2 receptor-expressing COS-7 cells caused rapid and specific phosphorylation of a single residue (Ser354) located in the cytoplasmic tail of the receptor. Agonist activation of AT2 receptors by angiotensin II (Ang II) also caused rapid PKC-dependent phosphorylation of Ser354 that was prevented by the AT2antagonist, PD123177, and by inhibitors of PKC. In cells coexpressing AT1 and AT2 receptors, Ang II-induced phosphorylation of the AT2 receptor was reduced by either PD123177 or the AT1 receptor antagonist, DuP753, and was abolished by treatment with both antagonists or with PKC inhibitors. These findings indicate that the AT2 receptor is rapidly phosphorylated via PKC during homologous activation by Ang II, and also undergoes heterologous PKC-dependent phosphorylation during activation of the AT1 receptor. The latter process may regulate the counteracting effects of AT2 receptors on growth responses to AT1 receptor activation.