The maturation of mammalian oocytes in vitro can be stimulated by gonadotropins (follicle-stimulating hormone, FSH) or their intrafollicular mediator, epidermal growth factor (EGF)-like peptide-amphiregulin (AREG). We have shown previously that in pig cumulus-oocyte complexes (COCs), FSH induces expression and the synthesis of AREG that binds to EGF receptor (EGFR) and activates the mitogen-activated protein kinase 3/1 (MAPK3/1) signaling pathway. However, in this study we found that FSH also caused a rapid activation of MAPK3/1 in the cumulus cells, which cannot be explained by the de novo synthesis of AREG. The rapid MAPK3/1 activation required EGFR tyrosine kinase (TK) activity, was sensitive to SRC proto-oncogene non-receptor tyrosine kinase (SRC)-family and protein kinase C (PKC) inhibitors, and was resistant to inhibitors of protein kinase A (PKA) and metalloproteinases. AREG also induced the rapid activation of MAPK3/1 in cumulus cells, but this activation was only dependent on the EGFR TK activity. We conclude that in cumulus cells, FSH induces a rapid activation of MAPK3/1 by the ligand-independent transactivation of EGFR, requiring SRC and PKC activities. This rapid activation of MAPK3/1 precedes the second mechanism participating in the generation and maintenance of active MAPK3/1-the ligand-dependent activation of EGFR depending on the synthesis of EGF-like peptides.
- MeSH
- aktivace transkripce MeSH
- amfiregulin metabolismus MeSH
- erbB receptory metabolismus MeSH
- extracelulárním signálem regulované MAP kinasy genetika MeSH
- folikuly stimulující hormon farmakologie MeSH
- IVM techniky MeSH
- kultivované buňky MeSH
- kumulární buňky cytologie účinky léků metabolismus MeSH
- mitogenem aktivovaná proteinkinasa 1 genetika MeSH
- mitogenem aktivovaná proteinkinasa 3 genetika MeSH
- oocyty cytologie účinky léků metabolismus MeSH
- prasata MeSH
- signální transdukce účinky léků MeSH
- skupina kinas odvozených od src-genu metabolismus MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH