ArticleThe Journal of biological chemistry2009
Leptin-dependent phosphorylation of PTEN mediates actin restructuring and activation of ATP-sensitive K+ channels.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Clathrin-associated SCYL2 contributes to the activation of PI3K/AKT signaling and tumorigenesis through PTEN phosphorylation in adult T-cell leukemia/lymphoma.Cancer gene therapy · 2026Article
- Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.Medicinal research reviews · 2022Review
- Phosphatidylinositol-3 kinase mediates the sweet suppressive effect of leptin in mouse taste cells.Journal of neurochemistry · 2021Article
- Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Leptin-induced Trafficking of KInternational journal of molecular sciences · 2019Review
- Leptin increases mitochondrial OPA1 via GSK3-mediated OMA1 ubiquitination to enhance therapeutic effects of mesenchymal stem cell transplantation.Cell death & disease · 2018Article
- Leptin-mediated ion channel regulation: PI3K pathways, physiological role, and therapeutic potential.Channels (Austin, Tex.) · 2016Review
- Leptin Elongates Hypothalamic Neuronal Cilia via Transcriptional Regulation and Actin Destabilization.The Journal of biological chemistry · 2015Article
- Valsartan Upregulates Kir2.1 in Rats Suffering from Myocardial Infarction via Casein Kinase 2.Cardiovascular drugs and therapy · 2015Article
- The CNS glucagon-like peptide-2 receptor in the control of energy balance and glucose homeostasis.American journal of physiology. Regulatory, integrative and comparative physiology · 2014Review
- Advanced pharmacotherapy evidenced by pathogenesis of autism spectrum disorder.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2014Review
- Leptin regulation of hippocampal synaptic function in health and disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014Review
- Leptin regulates KATP channel trafficking in pancreatic β-cells by a signaling mechanism involving AMP-activated protein kinase (AMPK) and cAMP-dependent protein kinase (PKA).The Journal of biological chemistry · 2013Article
- PTEN modulators: a patent review.Expert opinion on therapeutic patents · 2013Review
- Functional analysis of the protein phosphatase activity of PTEN.The Biochemical journal · 2012Article
- Enhanced GLP-1- and sulfonylurea-induced insulin secretion in islets lacking leptin signaling.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Differential acute and chronic effects of leptin on hypothalamic astrocyte morphology and synaptic protein levels.Endocrinology · 2011Article
- What Are the bona fide GSK3 Substrates?International journal of Alzheimer's disease · 2011Article
- Article
- Leptin-stimulated KATP channel trafficking: a new paradigm for β-cell stimulus-secretion coupling?IsletsArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Leptin activates multiple signaling pathways in cells, including the phosphatidylinositol 3-kinase pathway, indicating a degree of cross-talk with insulin signaling. The exact mechanisms by which leptin alters this signaling pathway and how it relates to functional outputs are unclear at present. A previous study has established that leptin inhibits the activity of the phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10), an important tumor suppressor and modifier of phosphoinositide signaling. In this study we demonstrate that leptin phosphorylates multiple sites on the C-terminal tail of PTEN in hypothalamic and pancreatic beta-cells, an action not replicated by insulin. Inhibitors of the protein kinases CK2 and glycogen synthase kinase 3 (GSK3) block leptin-mediated PTEN phosphorylation. PTEN phosphorylation mutants reveal the critical role these sites play in transmission of the leptin signal to F-actin depolymerization. CK2 and GSK3 inhibitors also prevent leptin-mediated F-actin depolymerization and consequent ATP-sensitive K(+) channel opening. GSK3 kinase activity is inhibited by insulin but not leptin in hypothalamic cells. Both hormones increase N-terminal GSK3 serine phosphorylation, but in hypothalamic cells this action of leptin is transient. Leptin, not insulin, increases GSK3 tyrosine phosphorylation in both cell types. These results demonstrate a significant role for PTEN in leptin signal transmission and identify GSK3 as a potential important signaling node contributing to divergent outputs for these hormones.
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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.