Homologous and heterologous phosphorylation of the AT2 angiotensin receptor by protein kinase C

Jesus A. Olivares-Reyes, Suman Jayadev, L. Hunyady, Kevin J. Catt, Roger D. Smith

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 AT2 antagonist, 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.

Original languageEnglish
Pages (from-to)1156-1161
Number of pages6
JournalMolecular Pharmacology
Volume58
Issue number5
Publication statusPublished - 2000

Fingerprint

Angiotensin Type 2 Receptor
Protein Kinase C
Phosphorylation
Angiotensin Receptors
Angiotensin Type 1 Receptor
Protein C Inhibitor
COS Cells
Phorbol Esters
Protein Kinase Inhibitors
Cytoplasmic and Nuclear Receptors
Phosphoric Monoester Hydrolases
Angiotensin II
Tyrosine
Phosphotransferases
Growth

ASJC Scopus subject areas

  • Pharmacology

Cite this

Olivares-Reyes, J. A., Jayadev, S., Hunyady, L., Catt, K. J., & Smith, R. D. (2000). Homologous and heterologous phosphorylation of the AT2 angiotensin receptor by protein kinase C. Molecular Pharmacology, 58(5), 1156-1161.

Homologous and heterologous phosphorylation of the AT2 angiotensin receptor by protein kinase C. / Olivares-Reyes, Jesus A.; Jayadev, Suman; Hunyady, L.; Catt, Kevin J.; Smith, Roger D.

In: Molecular Pharmacology, Vol. 58, No. 5, 2000, p. 1156-1161.

Research output: Contribution to journalArticle

Olivares-Reyes, JA, Jayadev, S, Hunyady, L, Catt, KJ & Smith, RD 2000, 'Homologous and heterologous phosphorylation of the AT2 angiotensin receptor by protein kinase C', Molecular Pharmacology, vol. 58, no. 5, pp. 1156-1161.
Olivares-Reyes, Jesus A. ; Jayadev, Suman ; Hunyady, L. ; Catt, Kevin J. ; Smith, Roger D. / Homologous and heterologous phosphorylation of the AT2 angiotensin receptor by protein kinase C. In: Molecular Pharmacology. 2000 ; Vol. 58, No. 5. pp. 1156-1161.
@article{c04095cb2347492fac231d39b8d69a46,
title = "Homologous and heterologous phosphorylation of the AT2 angiotensin receptor by protein kinase C",
abstract = "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 AT2 antagonist, 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.",
author = "Olivares-Reyes, {Jesus A.} and Suman Jayadev and L. Hunyady and Catt, {Kevin J.} and Smith, {Roger D.}",
year = "2000",
language = "English",
volume = "58",
pages = "1156--1161",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "5",

}

TY - JOUR

T1 - Homologous and heterologous phosphorylation of the AT2 angiotensin receptor by protein kinase C

AU - Olivares-Reyes, Jesus A.

AU - Jayadev, Suman

AU - Hunyady, L.

AU - Catt, Kevin J.

AU - Smith, Roger D.

PY - 2000

Y1 - 2000

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 AT2 antagonist, 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.

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 AT2 antagonist, 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.

UR - http://www.scopus.com/inward/record.url?scp=0033788636&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033788636&partnerID=8YFLogxK

M3 - Article

VL - 58

SP - 1156

EP - 1161

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 5

ER -