Extracellular Signal-regulated Kinase (ERK)-dependent Phosphorylation of Y-Box-binding Protein 1 (YB-1) Enhances Gene Expression in Granulosa Cells in Response to Follicle-stimulating Hormone (FSH).

摘要: Within the ovarian follicle, immature oocytes are surrounded and supported by granulosa cells (GCs). Stimulation of GCs FSH leads to their proliferation differentiation, events that necessary for fertility. activates multiple signaling pathways regulate genes follicular maturation. Herein, we investigated role Y-box-binding protein-1 (YB-1) within GCs. YB-1 is a nucleic acid binding protein regulates transcription translation. Our results show promotes an increase in phosphorylation on Ser(102) 15 min maintained at significantly increased levels until ∼8 h post treatment. FSH-stimulated YB-1(Ser(102)) prevented pretreatment with PKA-selective inhibitor PKA (PKI), MEK PD98059, or ribosomal S6 kinase-2 (RSK-2) BI-D1870. Thus, PKA-, ERK-, RSK-2-dependent. However, phosphatase 1 (PP1) tautomycin absence FSH; did not further phosphorylation. This result suggests major effect RSK-2 inhibit PP1 rather than directly phosphorylate coimmunoprecipitated PP1β catalytic subunit RSK-2. Transduction dephospho-adenoviral-YB-1(S102A) mutant induction Egfr, Cyp19a1, Inha, Lhcgr, Cyp11a1, Hsd17b1, Pappa mRNAs estradiol-17β production. Collectively, our reveal via ERK/RSK-2 pathway FSH-mediated expression target required maturation follicles preovulatory phenotype.