Antagonistic effects of phorbol esters on insulin regulation of insulin-like growth factor-binding protein-1 (IGFBP-1) but not glucose-6-phosphatase gene expression.

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  • Author(s): Patel S;Patel S; Lochhead PA; Rena G; Sutherland C
  • Source:
    The Biochemical journal [Biochem J] 2001 Nov 01; Vol. 359 (Pt 3), pp. 611-9.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Published by Portland Press on behalf of the Biochemical Society Country of Publication: England NLM ID: 2984726R Publication Model: Print Cited Medium: Print ISSN: 0264-6021 (Print) Linking ISSN: 02646021 NLM ISO Abbreviation: Biochem J Subsets: MEDLINE
    • Publication Information:
      Original Publication: London, UK : Published by Portland Press on behalf of the Biochemical Society
    • Subject Terms:
      Nerve Tissue Proteins*; Gene Expression Regulation/*drug effects ; Glucose-6-Phosphatase/*metabolism ; Insulin/*metabolism ; Insulin-Like Growth Factor Binding Protein 1/*metabolism ; Tetradecanoylphorbol Acetate/*pharmacology; Animals ; Benzamides/pharmacology ; Calcium-Calmodulin-Dependent Protein Kinases/metabolism ; Culture Media, Serum-Free ; Cyclic AMP/chemistry ; Cyclic AMP/pharmacology ; DNA-Binding Proteins/metabolism ; Dexamethasone/pharmacology ; Enzyme Inhibitors/pharmacology ; Forkhead Transcription Factors ; Gene Expression Regulation/physiology ; Glucocorticoids/pharmacology ; Glucose-6-Phosphatase/genetics ; Glycogen Synthase Kinase 3 ; Insulin-Like Growth Factor Binding Protein 1/genetics ; Mitogen-Activated Protein Kinases/metabolism ; Promoter Regions, Genetic/genetics ; Protein Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-akt ; Rats ; Ribosomal Protein S6 Kinases/metabolism ; Tetradecanoylphorbol Acetate/metabolism ; Transcription Factors/metabolism ; Tumor Cells, Cultured
    • Abstract:
      Glucose-6-phosphatase (G6Pase) and insulin-like growth factor-binding protein-1 (IGFBP-1) genes contain a homologous promoter sequence that is required for gene repression by insulin. Interestingly, this element interacts with members of the forkhead family of transcription factors [e.g. HNF3 (hepatic nuclear factor 3), FKHR (forkhead in rhabdomyosarcoma)] in vitro, while insulin promotes the phosphorylation and inactivation of FKHR in a phosphatidylinositol 3-kinase- and protein kinase B (PKB)-dependent manner. This mechanism has been proposed to underlie insulin action on G6Pase and IGFBP-1 gene transcription. However, we find that treatment of cells with phorbol esters mimics the effect of insulin on G6Pase, but not IGFBP-1, gene expression. Indeed, phorbol ester treatment actually blocks the ability of insulin to repress IGFBP-1 gene expression. In addition, the action of phorbol esters is significantly reduced by inhibition of the p42/p44 mitogen-activated protein (MAP) kinase pathway. However insulin-induced phosphorylation of PKB or FKHR is not affected by the presence of phorbol esters. Therefore we suggest that activation of p42/p44 MAP kinases will reduce the sensitivity of the IGFBP-1 gene promoter, but not the G6Pase gene promoter, to insulin. Importantly, the activation of PKB and phosphorylation of FKHR is not, in itself, sufficient to reduce IGFBP-1 gene expression in the presence of phorbol esters.
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    • Accession Number:
      0 (2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide)
      0 (Benzamides)
      0 (Culture Media, Serum-Free)
      0 (DNA-Binding Proteins)
      0 (Enzyme Inhibitors)
      0 (Forkhead Transcription Factors)
      0 (Glucocorticoids)
      0 (Insulin)
      0 (Insulin-Like Growth Factor Binding Protein 1)
      0 (Nerve Tissue Proteins)
      0 (Proto-Oncogene Proteins)
      0 (Transcription Factors)
      0 (Foxo1 protein, rat)
      7S5I7G3JQL (Dexamethasone)
      E0399OZS9N (Cyclic AMP)
      EC 2.7.1.- (phosphoenolpyruvate carboxylase kinase)
      EC 2.7.11.1 (Protein Serine-Threonine Kinases)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
      EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
      EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
      EC 2.7.11.26 (Glycogen Synthase Kinase 3)
      EC 3.1.3.9 (Glucose-6-Phosphatase)
      NI40JAQ945 (Tetradecanoylphorbol Acetate)
    • Publication Date:
      Date Created: 20011024 Date Completed: 20011213 Latest Revision: 20221207
    • Publication Date:
      20240829
    • Accession Number:
      PMC1222183
    • Accession Number:
      10.1042/0264-6021:3590611
    • Accession Number:
      11672436