A novel mechanism of FSH regulation of DNA synthesis in the granulosa cells of hamster preantral follicles: involvement of a protein kinase C-mediated MAP kinase 3/1 self-activation loop

Biology of Reproduction
Peixin Yang, Shyamal K Roy

Abstract

The objective was to reveal whether a protein kinase C (PKC [all isozymes])-mediated self-sustaining MAPK3/1 (3/1 extracellular signal regulated kinase 2/1, also known as ERK2/1) activation loop was necessary for FSH- or epidermal growth factor (EGF)-induced DNA synthesis in the granulosa cells of intact preantral follicles. For this purpose, hamster preantral follicles were cultured with FSH or EGF in the presence of selective kinase inhibitors FSH or EGF phosphorylated RAF1, MAP2K1, and MAPK3/1. However, a relatively higher dose of EGF was necessary to sustain the MAPK3/1 activity, which was essential for cyclin-dependent kinase 4 (CDK4) activation and DNA synthesis. In intact preantral follicles, FSH or EGF stimulated DNA synthesis only in the granulosa cells. Sustained activation of MAPK3/1 beyond 3 h was independent of EGFR kinase activity but dependent on PKC activity, which appeared to form a self-sustaining MAPK3/1 activation loop by activating RAF1, MAP2K1, and PLA2G4 (phospholipase A2 [all cytosolic isozymes]). Inhibition of PKC activity as late as 4 h after the administration of FSH or EGF arrested DNA synthesis, which corresponded with attenuated phosphorylation of RAF1 and MAPK3/1, thus suggesting an essential role...Continue Reading

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Citations

Dec 17, 2009·Reproduction, Fertility, and Development·Mario Binelli, Bruce D Murphy
Aug 13, 2008·Molecular and Cellular Endocrinology·Venkataraman SriramanRandall J Urban
Oct 15, 2013·Molecular and Cellular Endocrinology·Flavie LandomielEric Reiter
Feb 14, 2018·Journal of Molecular Endocrinology·Nandana Das, T Rajendra Kumar
May 20, 2020·Biology of Reproduction·Patricia G Tremblay, Marc-André Sirard
May 31, 2007·Molecular Endocrinology·Cheng-Guang LiangQing-Yuan Sun
Jul 21, 2011·Molecular Reproduction and Development·Ryusaku DeguchiStephen A Stricker
Jul 28, 2020·Animal Reproduction·Filiz Tepekoy, Gokhan Akkoyunlu

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