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Research ArticleENDOCRINE AND REPRODUCTIVE

Role of Protein Kinase C-Ras-MAPK p44/42 in Ethanol and Transforming Growth Factor-β3-Induced Basic Fibroblast Growth Factor Release from Folliculostellate Cells

Kirti Chaturvedi and Dipak K. Sarkar
Journal of Pharmacology and Experimental Therapeutics September 2005, 314 (3) 1346-1352; DOI: https://doi.org/10.1124/jpet.105.088302
Kirti Chaturvedi
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Dipak K. Sarkar
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Abstract

In the present study, we determined the interactive effects of ethanol and transforming growth factor β-3 (TGF-β3) on basic fibroblast growth factor (bFGF) release from folliculostellate (FS) cells and the role of the mitogen-activated protein kinase (MAPK) pathway in this interaction. We found that TGF-β3 and ethanol alone increased release of bFGF from FS cells, but together they showed markedly increased levels of bFGF compared with the individual effect. Ethanol and TGF-β3 alone moderately increased activation of MAPK p44/42, but together they produced marked activation of MAPK p44/42. TGF-β3 alone increased the activation of smad2. Ethanol did not activate smad2 or alter TGF-β3 activation of smad2. Pretreatment of FS cells with a mitogen-activated protein kinase kinase 1/2 inhibitor or with a protein kinase C (PKC) inhibitor suppressed the TGF-β3 and ethanol actions on MAPK p44/42 activation and bFGF release. Ethanol and TGF-β3, either alone or in combination, increased the levels of active Ras. Furthermore, the MAPK p44/42 activation by TGF-β3 and ethanol was blocked by overexpression of Ras N17, a dominant negative mutant of Ras p21. These data suggest that the PKC-activated Ras-dependent MAPK p44/42 pathway is involved in the cross talk between TGF-β3 and ethanol to increase bFGF release from FS cells.

Footnotes

  • This work was supported by National Institutes of Health Grant AA11591.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.105.088302.

  • ABBREVIATIONS: TGF-β3, transforming growth factor-β3; bFGF, basic fibroblast growth factor; FS, folliculostellate; TβRII, transforming growth factor-β3 type II receptor; TβRI, transforming growth factor-β3 type I receptor; MAPK, mitogen-activated protein kinase; PKC, protein kinase C; MEK, mitogen-activated protein kinase kinase; U0126, 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene; Bis, bisindolylmaleimide; DMSO, dimethyl sulfoxide; PAGE, polyacrylamide gel electrophoresis; GST, glutathione S-transferase; DAG, diacylglycerol.

    • Received April 20, 2005.
    • Accepted June 13, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 385 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 385, Issue 1
1 Apr 2023
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Research ArticleENDOCRINE AND REPRODUCTIVE

Role of Protein Kinase C-Ras-MAPK p44/42 in Ethanol and Transforming Growth Factor-β3-Induced Basic Fibroblast Growth Factor Release from Folliculostellate Cells

Kirti Chaturvedi and Dipak K. Sarkar
Journal of Pharmacology and Experimental Therapeutics September 1, 2005, 314 (3) 1346-1352; DOI: https://doi.org/10.1124/jpet.105.088302

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Research ArticleENDOCRINE AND REPRODUCTIVE

Role of Protein Kinase C-Ras-MAPK p44/42 in Ethanol and Transforming Growth Factor-β3-Induced Basic Fibroblast Growth Factor Release from Folliculostellate Cells

Kirti Chaturvedi and Dipak K. Sarkar
Journal of Pharmacology and Experimental Therapeutics September 1, 2005, 314 (3) 1346-1352; DOI: https://doi.org/10.1124/jpet.105.088302
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