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Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB.

Publication ,  Journal Article
Hagiwara, M; Alberts, A; Brindle, P; Meinkoth, J; Feramisco, J; Deng, T; Karin, M; Shenolikar, S; Montminy, M
Published in: Cell
July 10, 1992

We have examined the mechanism by which the transcriptional activity of the cAMP-responsive factor CREB is attenuated following induction with forskolin. Metabolic labeling studies reveal that, after an initial burst of phosphorylation in response to cAMP, CREB is dephosphorylated and transcription of the cAMP-responsive somatostatin gene is correspondingly reduced. The phosphatase inhibitor 1 protein and okadaic acid both prevented the dephosphorylation of CREB at Ser-133 in PC12 cells and also augmented the transcriptional response to cAMP. Of the four Ser/Thr phosphatases described to date, only PP-1 appears to be similarly inhibited by these agents. As PP-1 specifically dephosphorylates CREB at Ser-133 and inhibits cAMP-dependent transcription, we propose that this phosphatase is the major regulator of CREB activity in cAMP-responsive cells.

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Published In

Cell

DOI

ISSN

0092-8674

Publication Date

July 10, 1992

Volume

70

Issue

1

Start / End Page

105 / 113

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Somatostatin
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Okadaic Acid
  • Gene Expression Regulation
  • Ethers, Cyclic
  • Developmental Biology
  • DNA-Binding Proteins
  • Cyclic AMP Response Element-Binding Protein
 

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Hagiwara, M., Alberts, A., Brindle, P., Meinkoth, J., Feramisco, J., Deng, T., … Montminy, M. (1992). Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB. Cell, 70(1), 105–113. https://doi.org/10.1016/0092-8674(92)90537-m
Hagiwara, M., A. Alberts, P. Brindle, J. Meinkoth, J. Feramisco, T. Deng, M. Karin, S. Shenolikar, and M. Montminy. “Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB.Cell 70, no. 1 (July 10, 1992): 105–13. https://doi.org/10.1016/0092-8674(92)90537-m.
Hagiwara M, Alberts A, Brindle P, Meinkoth J, Feramisco J, Deng T, et al. Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB. Cell. 1992 Jul 10;70(1):105–13.
Hagiwara, M., et al. “Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB.Cell, vol. 70, no. 1, July 1992, pp. 105–13. Pubmed, doi:10.1016/0092-8674(92)90537-m.
Hagiwara M, Alberts A, Brindle P, Meinkoth J, Feramisco J, Deng T, Karin M, Shenolikar S, Montminy M. Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB. Cell. 1992 Jul 10;70(1):105–113.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

July 10, 1992

Volume

70

Issue

1

Start / End Page

105 / 113

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Somatostatin
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Okadaic Acid
  • Gene Expression Regulation
  • Ethers, Cyclic
  • Developmental Biology
  • DNA-Binding Proteins
  • Cyclic AMP Response Element-Binding Protein