ArticleProceedings of the National Academy of Sciences of the United States of America2012
PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03868202 (Follicle Stimulating Hormone), which is not on this map. Cited by 75 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Follicle Stimulating Hormone (FSH) Glycosylation in Women: Effect of Estradiol
Who cites it
75 citing papers in PubMed, 139 citations in OpenAlex.
- Molecular analysis of a mutated FSH receptor detected in a patient with spontaneous ovarian hyperstimulation syndrome.PloS one · 2013Trial
- Infection-Dependent Modulation of the Host Adaptor Gab2 During Chlamydia trachomatis Intracellular Development.Microbiology and immunology · 2026Article
- Fosl2 Regulates FSH-Dependent Follicle Maturation Through Feedback Amplification of FSH/FSHR Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Vitamin K as an Endocrine Modulator: Mechanistic Links to Glucose Metabolism and Beyond.Nutrients · 2026Review
- FSH Receptor Asn680Ser Polymorphism Modulates Intrafollicular Nitric Oxide Bioavailability and Ovarian Responsiveness During IVF.International journal of molecular sciences · 2026Article
- Unveiling the role of the PI3K/Akt signaling pathway in follicular development and non-malignant ovarian dysfunction: a comprehensive review.Journal of ovarian research · 2026Review
- Decoding molecular signatures and identifying therapeutic targets in triple-negative breast cancer subtypes using omics and network analysis.Scientific reports · 2025Article
- Bisphenol A diglycidyl ether-induced DNA methylation abnormalities may disrupt testis development in adult male zebrafish.Environmental analysis, health and toxicology · 2025Article
- Integrated analysis of microRNA and mRNA interactions regulating fecundity in the ovaries of two distinct sheep breeds.BMC genomics · 2025Article
- The effect of visfatin on the transcriptomic profile of porcine anterior pituitary cells during periimplantation period.Scientific reports · 2025Article
- Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization.Clinical and experimental reproductive medicine · 2025Article
- Effects of atrazine on the HPG and HPA axes and steroidogenic pathways in females: relevance to reproductive function and breast, ovarian and uterine cancer.Frontiers in toxicology · 2025Review
- G protein-coupled receptors in prostate cancer: research progress and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Linoleic acid metabolite 13-Hydroxyoctadecadienoic acid as a biphasic ferroptosis modulator in granulosa cells: multi-omics analysis of ovine atretic follicles.Frontiers in cell and developmental biology · 2025Article
- An Update on Physiopathological Roles of Akt in the ReprodAKTive Mammalian Ovary.Life (Basel, Switzerland) · 2024Review
- Ovarian Hyperstimulation syndrome combined with hypothyroidism: a comprehensive review.Journal of ovarian research · 2024Review
- Article
- Mitoguardin 1 and 2 promote granulosa cell proliferation by activating AKT and regulating the Hippo-YAP1 signaling pathway.Cell death & disease · 2023Article
- HucMSC-EVs Facilitate In Vitro Development of Maternally Aged Preantral Follicles and Oocytes.Stem cell reviews and reports · 2023Article
- Oogenesis in Women: From Molecular Regulatory Pathways and Maternal Age to Stem Cells.International journal of molecular sciences · 2023Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Controlled maturation of ovarian follicles is necessary for fertility. Follicles are restrained at an immature stage until stimulated by FSH secreted by pituitary gonadotropes. FSH acts on granulosa cells within the immature follicle to inhibit apoptosis, promote proliferation, stimulate production of steroid and protein hormones, and induce ligand receptors and signaling intermediates. The phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) pathway is a pivotal signaling corridor necessary for transducing the FSH signal. We report that protein kinase A (PKA) mediates the actions of FSH by signaling through multiple targets to activate PI3K/AKT. PKA uses a route that promotes phosphorylation of insulin receptor substrate-1 (IRS-1) on Tyr(989), a canonical binding site for the 85-kDa regulatory subunit of PI3K that allosterically activates the catalytic subunit. PI3K activation leads to activation of AKT through phosphorylation of AKT on Thr(308) and Ser(473). The adaptor growth factor receptor bound protein 2-associated binding protein 2 (GAB2) is present in a preformed complex with PI3K heterodimer and IRS-1, it is an A-kinase anchoring protein that binds the type I regulatory subunit of PKA, and it is phosphorylated by PKA on Ser(159). Overexpression of GAB2 enhances FSH-stimulated AKT phosphorylation. GAB2, thus, seems to coordinate signals from the FSH-stimulated rise in cAMP that leads to activation of PI3K/AKT. The ability of PKA to commandeer IRS-1 and GAB2, adaptors that normally integrate receptor/nonreceptor tyrosine kinase signaling into PI3K/AKT, reveals a previously unrecognized route for PKA to activate a pathway that promotes proliferation, inhibits apoptosis, enhances translation, and initiates differentiation of granulosa cells.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.