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PMID:14605008

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Citation

Chaturvedi, K and Sarkar, DK (2004) Involvement of protein kinase C-dependent mitogen-activated protein kinase p44/42 signaling pathway for cross-talk between estradiol and transforming growth factor-beta3 in increasing basic fibroblast growth factor in folliculostellate cells. Endocrinology 145:706-15

Abstract

We have recently shown that TGF-beta3, in the presence of estradiol, increases the release of basic fibroblast growth factor (bFGF) from folliculostellate (FS) cells in the pituitary. We determined the interactive effects of TGF-beta3 and estradiol on bFGF production and release from FS cells, and the role of the MAPK pathway in TGF-beta3 and estradiol interaction. We found that TGF-beta3 and estradiol alone moderately increased cell content and release of bFGF from FS cells; but together, they markedly increased the peptide. Estradiol and TGF-beta3 alone moderately activated MAPK p44/42; together they produced marked activation of MAPK p44/42. Pretreatment of FS cells with an MAPK kinase 1/2 inhibitor or with protein kinase C inhibitors suppressed the activation of MAPK p44/42, bFGF release, and protein level increases, all of which were induced by TGF-beta3 and estradiol. Estradiol and TGF-beta3, either alone or in combination, increased the levels of active Ras. Furthermore, bFGF induction by TGF-beta3 and estradiol was blocked by overexpression of Ras N17, a dominant negative mutant of Ras p21. Estrogen receptor blocker ICI 182,780 failed to prevent estrogen's and TGF-beta3's effects on bFGF. These data suggest that an estradiol receptor-independent protein kinase C- activated Ras-dependent MAPK pathway is involved in the cross-talk between TGF-beta3 and estradiol to increase bFGF production and/or release from FS cells.

Links

PubMed PMC2895416 Online version:10.1210/en.2003-1063

Keywords

Animals; Cell Line; Drug Interactions; Enzyme Activation/drug effects; Enzyme Inhibitors/pharmacology; Estradiol/analogs & derivatives; Estradiol/pharmacology; Female; Fibroblast Growth Factor 2/metabolism; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases/antagonists & inhibitors; Mitogen-Activated Protein Kinases/metabolism; Phosphorylation; Pituitary Gland, Anterior/cytology; Pituitary Gland, Anterior/drug effects; Pituitary Gland, Anterior/metabolism; Protein Kinase C/metabolism; Rats; Rats, Inbred F344; Receptors, Estrogen/antagonists & inhibitors; Signal Transduction; Transforming Growth Factor beta/pharmacology; Transforming Growth Factor beta3

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:TGFB3

involved_in

GO:0000187: activation of MAPK activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:TGFB3

involved_in

GO:0043627: response to estrogen

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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