ArticleMolecular endocrinology (Baltimore, Md.)2008
Luteinizing hormone receptor activation in ovarian granulosa cells promotes protein kinase A-dependent dephosphorylation of microtubule-associated protein 2D.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Intercellular cyclic nucleotide dynamics mediate oocyte meiosis in mammalian preovulatory follicles.Current topics in developmental biology · 2026Review
- Testing the function of phosphoprotein phosphatases modified by luteinizing hormone signaling in mouse ovarian follicles: an update†.Biology of reproduction · 2025Article
- Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase†.Biology of reproduction · 2024Article
- B56δ long-disordered arms form a dynamic PP2A regulation interface coupled with global allostery and Jordan's syndrome mutations.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase.bioRxiv : the preprint server for biology · 2023Article
- Disease mutations and phosphorylation alter the allosteric pathways involved in autoinhibition of protein phosphatase 2A.The Journal of chemical physics · 2023Article
- Extended regulation interface coupled to the allosteric network and disease mutations in the PP2A-B56δ holoenzyme.bioRxiv : the preprint server for biology · 2023Article
- cAMP-Dependent Signaling and Ovarian Cancer.Cells · 2022Review
- Cyclic AMP links luteinizing hormone signaling to dephosphorylation and inactivation of the NPR2 guanylyl cyclase in ovarian follicles†.Biology of reproduction · 2021Article
- Cellular Heterogeneity of the Luteinizing Hormone Receptor and Its Significance for Cyclic GMP Signaling in Mouse Preovulatory Follicles.Endocrinology · 2020Article
- Mechanistic insight into how gonadotropin hormone receptor complexes direct signaling†.Biology of reproduction · 2020Review
- β-Adrenergic regulation of cardiac type 2A protein phosphatase through phosphorylation of regulatory subunit B56δ at S573.Journal of molecular and cellular cardiology · 2018Article
- Regulation of Mammalian Oocyte Meiosis by Intercellular Communication Within the Ovarian Follicle.Annual review of physiology · 2017Review
- Follicle-Stimulating Hormone (FSH)-dependent Regulation of Extracellular Regulated Kinase (ERK) Phosphorylation by the Mitogen-activated Protein (MAP) Kinase Phosphatase MKP3.The Journal of biological chemistry · 2016Article
- The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kinase 3β Interaction Protein (GSKIP) Regulates β-Catenin through Its Interactions with Both Protein Kinase A (PKA) and GSK3β.The Journal of biological chemistry · 2016Article
- Dephosphorylation of MAP2D enhances its binding to vimentin in preovulatory ovarian granulosa cells.Journal of cell science · 2016Article
- Luteinizing Hormone Causes Phosphorylation and Activation of the cGMP Phosphodiesterase PDE5 in Rat Ovarian Follicles, Contributing, Together with PDE1 Activity, to the Resumption of Meiosis.Biology of reproduction · 2016Article
- Insulin Receptor Substrate 1, the Hub Linking Follicle-stimulating Hormone to Phosphatidylinositol 3-Kinase Activation.The Journal of biological chemistry · 2016Article
- Luteinizing hormone: Evidence for direct action in the CNS.Hormones and behavior · 2015Review
- Hypothalamic-pituitary-gonadal axis involvement in learning and memory and Alzheimer's disease: more than "just" estrogen.Frontiers in endocrinology · 2015Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The actions of LH to induce ovulation and luteinization of preovulatory follicles are mediated principally by activation of cAMP-dependent protein kinase (PKA) in granulosa cells. PKA activity is targeted to specific locations in many cells by A kinase-anchoring proteins (AKAPs). We previously showed that FSH induces expression of microtubule-associated protein (MAP) 2D, an 80-kDa AKAP, in rat granulosa cells, and that MAP2D coimmunoprecipitates with PKA-regulatory subunits in these cells. Here we report a rapid and targeted dephosphorylation of MAP2D at Thr256/Thr259 after treatment with human chorionic gonadotropin, an LH receptor agonist. This event is mimicked by treatment with forskolin or a cAMP analog and is blocked by the PKA inhibitor myristoylated-PKI, indicating a role for cAMP and PKA signaling in phosphoregulation of granulosa cell MAP2D. Furthermore, we show that Thr256/Thr259 dephosphorylation is blocked by the protein phosphatase 2A (PP2A) inhibitor, okadaic acid, and demonstrate interactions between MAP2D and PP2A by coimmunoprecipitation and microcystin-agarose pull-down. We also show that MAP2D interacts with glycogen synthase kinase (GSK) 3beta and is phosphorylated at Thr256/Thr259 by this kinase in the basal state. Increased phosphorylation of GSK3beta at Ser9 and the PP2A B56delta subunit at Ser566 is observed after treatment with human chorionic gonadotropin and appears to result in LH receptor-mediated inhibition of GSK3beta and activation of PP2A, respectively. Taken together, these results show that the phosphorylation status of the AKAP MAP2D is acutely regulated by LH receptor-mediated modulation of kinase and phosphatase activities via PKA.
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