ArticleProceedings of the National Academy of Sciences of the United States of America2008
Disruption of the RIIbeta subunit of PKA reverses the obesity syndrome of Agouti lethal yellow mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs.Molecular psychiatry · 2011Trial
- Complementary structure of statistical significance and predictive relevance in explainable machine learning-based transcriptomic tissue classification of Hanwoo cattle.Frontiers in genetics · 2026Article
- The microprotein C16orf74/MICT1 promotes thermogenesis in brown adipose tissue.The EMBO journal · 2025Article
- A bioluminescent and homogeneous assay for monitoring GPCR-mediated cAMP modulation and PDE activity.Scientific reports · 2024Article
- RIIβ-PKA in GABAergic Neurons of Dorsal Median Hypothalamus Governs White Adipose Browning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Role of Neuropeptide Y in the Nucleus Accumbens.International journal of molecular sciences · 2021Review
- PKA functions in metabolism and resistance to obesity: lessons from mouse and human studies.The Journal of endocrinology · 2020Review
- Whole-genome resequencing reveals signatures of selection and timing of duck domestication.GigaScience · 2018Article
- Hypothalamic PKA regulates leptin sensitivity and adiposity.Nature communications · 2015Article
- Single Turnover Autophosphorylation Cycle of the PKA RIIβ Holoenzyme.PLoS biology · 2015Article
- Article
- Local cAMP signaling in disease at a glance.Journal of cell science · 2013Review
- cAMP/PKA signaling defects in tumors: genetics and tissue-specific pluripotential cell-derived lesions in human and mouse.Molecular and cellular endocrinology · 2013Review
- Deficiency of the RIIβ subunit of PKA affects locomotor activity and energy homeostasis in distinct neuronal populations.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Assembly of allosteric macromolecular switches: lessons from PKA.Nature reviews. Molecular cell biology · 2012Review
- Human tau may modify glucocorticoids-mediated regulation of cAMP-dependent kinase and phosphorylated cAMP response element binding protein.Neurochemical research · 2012Article
- Melanocortin-induced PKA activation inhibits AMPK activity via ERK-1/2 and LKB-1 in hypothalamic GT1-7 cells.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Neuropeptide Y signaling modulates the expression of ethanol-induced behavioral sensitization in mice.Addiction biology · 2012Article
- Structure and allostery of the PKA RIIβ tetrameric holoenzyme.Science (New York, N.Y.) · 2012Article
- Adiponectin inhibits lipolysis in mouse adipocytes.Diabetes · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Agouti lethal yellow (A(y)) mice express agouti ectopically because of a genetic rearrangement at the agouti locus. The agouti peptide is a potent antagonist of the melanocortin 4 receptor (MC4R) expressed in neurons, and this leads to hyperphagia, hypoactivity, and increased fat mass. The MC4R signals through Gs and is thought to stimulate the production of cAMP and activation of downstream cAMP effector molecules such as PKA. Disruption of the RIIbeta regulatory subunit gene of PKA results in release of the active catalytic subunit and an increase in basal PKA activity in cells where RIIbeta is highly expressed. Because RIIbeta is expressed in neurons including those in the hypothalamic nuclei where MC4R is prominent we tested the possibility that the RIIbeta knockout might rescue the body weight phenotypes of the A(y) mice. Disruption of the RIIbeta PKA regulatory subunit gene in mice leads to a 50% reduction in white adipose tissue and resistance to diet-induced obesity and hyperglycemia. The RIIbeta mutation rescued the elevated body weight, hyperphagia, and obesity of A(y) mice. Partial rescue of the A(y) phenotypes was even observed on an RIIbeta heterozygote background. These results suggest that the RIIbeta gene mutation alters adiposity and locomotor activity by modifying PKA signaling pathways downstream of the agouti antagonism of MC4R in the hypothalamus.
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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.