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Angiotensin II type 2 receptor mediates programmed cell death.

Publication ,  Journal Article
Yamada, T; Horiuchi, M; Dzau, VJ
Published in: Proc Natl Acad Sci U S A
January 9, 1996

The function of the recently discovered angiotensin II type 2 (AT2) receptor remains elusive. This receptor is expressed abundantly in fetus, but scantily in adult tissues except brain, adrenal medulla, and atretic ovary. In this study, we demonstrated that this receptor mediates programmed cell death (apoptosis). We observed this effect in PC12W cells (rat pheochromocytoma cell line) and R3T3 cells (mouse fibroblast cell line), which express abundant AT2 receptor but not AT1 receptor. The cellular mechanism appears to involve the dephosphorylation of mitogen-activated protein kinase (MAP kinase). Vanadate, a protein-tyrosine-phosphatase inhibitor, attenuated the dephosphorylation of MAP kinases by the AT2 receptor and restored the apoptotic changes. Antisense oligonucleotide to MAP kinase phosphatase 1 inhibited the AT2 receptor-mediated MAP kinase dephosphorylation and blocked the AT2 receptor-mediated apoptosis. These results suggest that protein-tyrosine-phosphatase, including MAP kinase phosphatase 1 activated by the AT2 receptor, is involved in apoptosis. We hypothesize that this apoptotic function of the AT2 receptor may play an important role in developmental biology and pathophysiology.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

January 9, 1996

Volume

93

Issue

1

Start / End Page

156 / 160

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Angiotensin
  • Rats
  • Protein Tyrosine Phosphatases
  • Protein Phosphatase 1
  • Phosphoprotein Phosphatases
  • PC12 Cells
  • Oligonucleotides, Antisense
 

Citation

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Yamada, T., Horiuchi, M., & Dzau, V. J. (1996). Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci U S A, 93(1), 156–160. https://doi.org/10.1073/pnas.93.1.156
Yamada, T., M. Horiuchi, and V. J. Dzau. “Angiotensin II type 2 receptor mediates programmed cell death.Proc Natl Acad Sci U S A 93, no. 1 (January 9, 1996): 156–60. https://doi.org/10.1073/pnas.93.1.156.
Yamada T, Horiuchi M, Dzau VJ. Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):156–60.
Yamada, T., et al. “Angiotensin II type 2 receptor mediates programmed cell death.Proc Natl Acad Sci U S A, vol. 93, no. 1, Jan. 1996, pp. 156–60. Pubmed, doi:10.1073/pnas.93.1.156.
Yamada T, Horiuchi M, Dzau VJ. Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):156–160.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

January 9, 1996

Volume

93

Issue

1

Start / End Page

156 / 160

Location

United States

Related Subject Headings

  • Transfection
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Angiotensin
  • Rats
  • Protein Tyrosine Phosphatases
  • Protein Phosphatase 1
  • Phosphoprotein Phosphatases
  • PC12 Cells
  • Oligonucleotides, Antisense