ArticleEndocrinology2011
The adapter protein APPL1 links FSH receptor to inositol 1,4,5-trisphosphate production and is implicated in intracellular Ca(2+) mobilization.
Article in Endocrinology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Inositol and Non-Alcoholic Fatty Liver Disease: A Systematic Review on Deficiencies and Supplementation.Nutrients · 2020Pooled it
- Comparative analysis of PI3K-AKT and MEK-ERK1/2 signaling-driven molecular changes in granulosa cells.Reproduction (Cambridge, England) · 2025Article
- Polycystic Ovary Syndrome as Metabolic Disease: New Insights on Insulin Resistance.TouchREVIEWS in endocrinology · 2023Review
- Biological Assay to Determine Gonadotropin Potency: From In Vivo to In Vitro Sustainable Method.International journal of molecular sciences · 2023Article
- Putative Complementary Compounds to Counteract Insulin-Resistance in PCOS Patients.Biomedicines · 2022Review
- RAF1 mediates the FSH signaling pathway as a downstream molecule to stimulate estradiol synthesis and secretion in mouse ovarian granulosa cells.Annals of translational medicine · 2022Article
- Myo-inositol for insulin resistance, metabolic syndrome, polycystic ovary syndrome and gestational diabetes.Open heart · 2022Article
- Overview of follicle stimulating hormone and its receptors in reproduction and in stem cells and cancer stem cells.International journal of biological sciences · 2022Review
- ERβ Regulation of Gonadotropin Responses during Folliculogenesis.International journal of molecular sciences · 2021Review
- Recent advances in understanding gonadotropin signaling.Faculty reviews · 2021Review
- Review
- Inositols and metabolic disorders: From farm to bedside.Journal of traditional and complementary medicine · 2020Review
- In Vitro Impact of FSH Glycosylation Variants on FSH Receptor-stimulated Signal Transduction and Functional Selectivity.Journal of the Endocrine Society · 2020Article
- Mechanistic insight into how gonadotropin hormone receptor complexes direct signaling†.Biology of reproduction · 2020Review
- Clinical and Metabolic Effects of Alpha-Lipoic Acid Associated with Two Different Doses of Myo-Inositol in Women with Polycystic Ovary Syndrome.International journal of endocrinology · 2020Article
- Molecular Mechanisms of Action of FSH.Frontiers in endocrinology · 2019Review
- Gonadotropin receptor variants are linked to cumulative live birth rate after in vitro fertilization.Journal of assisted reproduction and genetics · 2019Article
- Biased Signaling and Allosteric Modulation at the FSHR.Frontiers in endocrinology · 2019Review
- Endocytosis is required for CThe Journal of biological chemistry · 2018Article
- Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.Journal of endocrinological investigation · 2018Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
FSH binds to its receptor (FSHR) on target cells in the ovary and testis, to regulate oogenesis and spermatogenesis, respectively. The signaling cascades activated after ligand binding are extremely complex and have been shown to include protein kinase A, mitogen-activated protein kinase, phosphatidylinositol 3-kinase/protein kinase B, and inositol 1,4,5-trisphosphate-mediated calcium signaling pathways. The adapter protein APPL1 (Adapter protein containing Pleckstrin homology domain, Phosphotyrosine binding domain and Leucine zipper motif), which has been linked to an assortment of other signaling proteins, was previously identified as an interacting protein with FSHR. Thus, alanine substitution mutations in the first intracellular loop of FSHR were generated to determine which residues are essential for FSHR-APPL1 interaction. Three amino acids were essential; when any one of them was altered, APPL1 association with FSHR mutants was abrogated. Two of the mutants (L377A and F382A) that displayed poor cell-surface expression were not studied further. Substitution of FSHR-K376A did not affect FSH binding or agonist-stimulated cAMP production in either transiently transfected human embryonic kidney cells or virally transduced human granulosa cells (KGN). In the KGN line, as well as primary cultures of rat granulosa cells transduced with wild type or mutant receptor, FSH-mediated progesterone or estradiol production was not affected by the mutation. However, in human embryonic kidney cells inositol 1,4,5-trisphosphate production was curtailed and KGN cells transduced with FSHR-K376A evidenced reduced Ca(2+) mobilization from intracellular stores after FSH treatment.
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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.