TY - JOUR T1 - Homologous and Heterologous Phosphorylation of the AT<sub>2</sub> Angiotensin Receptor by Protein Kinase C JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1156 LP - 1161 DO - 10.1124/mol.58.5.1156 VL - 58 IS - 5 AU - Jesus A. Olivares-Reyes AU - Suman Jayadev AU - László Hunyady AU - Kevin J. Catt AU - Roger D. Smith Y1 - 2000/11/01 UR - http://molpharm.aspetjournals.org/content/58/5/1156.abstract N2 - 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. ER -