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Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis.

Publication ,  Journal Article
Horiuchi, M; Hayashida, W; Kambe, T; Yamada, T; Dzau, VJ
Published in: J Biol Chem
July 25, 1997

We examined the cellular and signaling mechanism of angiotensin II (Ang II) type 2 (AT2) receptor-induced apoptosis in PC12W (rat pheochromocytoma cell line) cells that express abundant AT2 receptor but not Ang II type 1 receptor. In these cells, nerve growth factor (NGF) inhibited the internucleosomal DNA fragmentation induced by serum depletion, whereas Ang II antagonized this NGF cell survival action and induced apoptosis. We studied the mechanism of NGF and AT2 receptor interaction on apoptosis by examining their effects on the survival factor Bcl-2. AT2 receptor activation did affect intracellular Bcl-2 protein levels. Bcl-2 phosphorylation was stimulated by NGF, whereas AT2 receptor activation blocked this NGF effect. Pretreatment with antisense oligonucleotide of mitogen-activated protein (MAP) kinase phosphatase-1 enhanced the effects of NGF on MAP kinase activation and Bcl-2 phosphorylation but attenuated the inhibitory effects of AT2 receptor on MAP kinase, Bcl-2 phosphorylation, and apoptosis. Taken together, these results suggest that MAP kinase plays a critical role in inhibiting apoptosis by phosphorylating Bcl-2. The AT2 receptor inhibits MAP kinase activation, resulting in the inactivation of Bcl-2 and the induction of apoptosis.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 25, 1997

Volume

272

Issue

30

Start / End Page

19022 / 19026

Location

United States

Related Subject Headings

  • Receptors, Angiotensin
  • Receptor, Angiotensin, Type 2
  • Rats
  • Proto-Oncogene Proteins c-bcl-2
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Phosphatase 1
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • PC12 Cells
 

Citation

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ICMJE
MLA
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Horiuchi, M., Hayashida, W., Kambe, T., Yamada, T., & Dzau, V. J. (1997). Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis. J Biol Chem, 272(30), 19022–19026. https://doi.org/10.1074/jbc.272.30.19022
Horiuchi, M., W. Hayashida, T. Kambe, T. Yamada, and V. J. Dzau. “Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis.J Biol Chem 272, no. 30 (July 25, 1997): 19022–26. https://doi.org/10.1074/jbc.272.30.19022.
Horiuchi M, Hayashida W, Kambe T, Yamada T, Dzau VJ. Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis. J Biol Chem. 1997 Jul 25;272(30):19022–6.
Horiuchi, M., et al. “Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis.J Biol Chem, vol. 272, no. 30, July 1997, pp. 19022–26. Pubmed, doi:10.1074/jbc.272.30.19022.
Horiuchi M, Hayashida W, Kambe T, Yamada T, Dzau VJ. Angiotensin type 2 receptor dephosphorylates Bcl-2 by activating mitogen-activated protein kinase phosphatase-1 and induces apoptosis. J Biol Chem. 1997 Jul 25;272(30):19022–19026.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 25, 1997

Volume

272

Issue

30

Start / End Page

19022 / 19026

Location

United States

Related Subject Headings

  • Receptors, Angiotensin
  • Receptor, Angiotensin, Type 2
  • Rats
  • Proto-Oncogene Proteins c-bcl-2
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Phosphatase 1
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • PC12 Cells