How Protein Kinase A Activates Canonical Tyrosine Kinase Signaling Pathways To Promote Granulosa Cell Differentiation

摘要: Protein kinase A (PKA) has recently been shown to mimic the actions of follicle-stimulating hormone (FSH) by activating signaling pathways that promote granulosa cell (GC) differentiation, such as phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase/extracellular signal-regulated (MAPK/ERK). We sought elucidate mechanism which PKA, a Ser/Thr kinase, intersected PI3K/AKT MAPK/ERK are canonically activated receptor tyrosine kinases (RTKs). Our results show for both these pathways, RTK is active in absence FSH yet down commence transcriptional responses requires FSH-stimulated PKA activation. For initiates regulating activity phosphatase (PP). pathway, activates PP1 complexed with insulinlike growth factor 1 (IGF-1R) insulin substrate (IRS1) dephosphorylate Ser residues on IRS1, authorizing phosphorylation IRS1 IGF-1R activate PI3K. Treatment GCs exogenous IGF-1 synergistic Tyr resulting gene The PI3K conserved preovulatory GCs, MCF7 breast cancer cells, FRTL thyroid cells. promotes inactivation MAPK (MKP) dual specificity (DUSP) MKP3/DUSP6 permit MEK-phosphorylated ERK accumulate downstream epidermal receptor. Thus, two central regulate expression via intersects canonical RTK-regulated modulating PPs.