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Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3.

Publication ,  Journal Article
Piwien-Pilipuk, G; Van Mater, D; Ross, SE; MacDougald, OA; Schwartz, J
Published in: J Biol Chem
June 1, 2001

Growth hormone (GH) regulates transcription factors associated with c-fos, including C/EBPbeta. Two forms of C/EBPbeta, liver-activating protein (LAP) and liver inhibitory protein (LIP), are dephosphorylated in GH-treated 3T3-F442A fibroblasts. GH-induced dephosphorylation of LAP and LIP is reduced when cells are preincubated with phosphatidylinositol 3'-kinase (PI3K) inhibitors. GH activates Akt and inhibits glycogen synthase kinase-3 (GSK-3). Lithium, a GSK-3 inhibitor, increases GH-dependent dephosphorylation of LAP and LIP. Both are in vitro substrates of GSK-3, suggesting that GSK-3 inactivation contributes to GH-promoted dephosphorylation of C/EBPbeta. Alkaline phosphatase increases binding of LAP homodimers and decreases binding of LIP homodimers to c-fos, suggesting that dephosphorylation of C/EBPbeta modifies their ability to bind DNA. Both alkaline phosphatase- and GH-mediated dephosphorylation comparably increase binding of endogenous LAP in 3T3-F442A cells. In cells overexpressing LAP and GSK-3, LAP binding decreases, suggesting that GSK-3-mediated phosphorylation interferes with LAP binding. Expression of constitutively active GSK-3 reduced GH-stimulated c-fos promoter activity. These studies indicate that PI3K/Akt/GSK-3 mediates signaling between GH receptor and the nucleus, promoting dephosphorylation of C/EBPbeta. Dephosphorylation increases binding of LAP complexes to the c-fos promoter and may contribute to the participation of C/EBPbeta in GH-stimulated c-fos expression.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

June 1, 2001

Volume

276

Issue

22

Start / End Page

19664 / 19671

Location

United States

Related Subject Headings

  • Transfection
  • Transcriptional Activation
  • Time Factors
  • Signal Transduction
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Promoter Regions, Genetic
 

Citation

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Piwien-Pilipuk, G., Van Mater, D., Ross, S. E., MacDougald, O. A., & Schwartz, J. (2001). Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3. J Biol Chem, 276(22), 19664–19671. https://doi.org/10.1074/jbc.M010193200
Piwien-Pilipuk, G., D. Van Mater, S. E. Ross, O. A. MacDougald, and J. Schwartz. “Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3.J Biol Chem 276, no. 22 (June 1, 2001): 19664–71. https://doi.org/10.1074/jbc.M010193200.
Piwien-Pilipuk G, Van Mater D, Ross SE, MacDougald OA, Schwartz J. Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3. J Biol Chem. 2001 Jun 1;276(22):19664–71.
Piwien-Pilipuk, G., et al. “Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3.J Biol Chem, vol. 276, no. 22, June 2001, pp. 19664–71. Pubmed, doi:10.1074/jbc.M010193200.
Piwien-Pilipuk G, Van Mater D, Ross SE, MacDougald OA, Schwartz J. Growth hormone regulates phosphorylation and function of CCAAT/enhancer-binding protein beta by modulating Akt and glycogen synthase kinase-3. J Biol Chem. 2001 Jun 1;276(22):19664–19671.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

June 1, 2001

Volume

276

Issue

22

Start / End Page

19664 / 19671

Location

United States

Related Subject Headings

  • Transfection
  • Transcriptional Activation
  • Time Factors
  • Signal Transduction
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Promoter Regions, Genetic