Role of protein kinase C-Ras-MAPK p44/42 in ethanol and transforming growth factor-beta3-induced basic fibroblast growth factor release from folliculostellate cells.
In the present study, we determined the interactive effects of ethanol and transforming growth factor beta-3 (TGF-beta3) 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-beta3 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-beta3 alone moderately increased activation of MAPK p44/42, but together they produced marked activation of MAPK p44/42. TGF-beta3 alone increased the activation of smad2. Ethanol did not activate smad2 or alter TGF-beta3 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-beta3 and ethanol actions on MAPK p44/42 activation and bFGF release. Ethanol and TGF-beta3, either alone or in combination, increased the levels of active Ras. Furthermore, the MAPK p44/42 activation by TGF-beta3 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-beta3 and ethanol to increase bFGF release from FS cells.
Chaturvedi
Kirti
K
Endocrinology Program and Department of Animal Science, Rutgers, The State University of New Jersey, New Brunswick, USA.
Sarkar
Dipak K
DK
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology*; D010766:Phosphorylation; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D051899:Smad2 Protein; D015534:Trans-Activators / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053782:Transforming Growth Factor beta3; D018631:ras Proteins / Q000502:physiology*
D004268:DNA-Binding Proteins; D051899:Smad2 Protein; C497784:Smad2 protein, rat; C509046:Tgfb3 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D016222:Fibroblast Growth Factor 2; D000431:Ethanol; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D018631:ras Proteins