ArticleProceedings of the National Academy of Sciences of the United States of America2010
Suppressor of MEK null (SMEK)/protein phosphatase 4 catalytic subunit (PP4C) is a key regulator of hepatic gluconeogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 76 citations in OpenAlex.
- A multilayered regulatory network mediated by protein phosphatase 4 controls carbon catabolite repression and de-repression in Magnaporthe oryzae.Communications biology · 2025Article
- SMEK1 ablation promotes glucose uptake and improves obesity-related metabolic dysfunction via AMPK signaling pathway.American journal of physiology. Endocrinology and metabolism · 2024Article
- The triglyceride catabolism regulated by a serine/threonine protein phosphatase, Smek1, is required for development and plant infection in Magnaporthe oryzae.Molecular plant pathology · 2023Article
- Biological functions of CRTC2 and its role in metabolism-related diseases.Journal of cell communication and signaling · 2023Review
- SMEK1 promotes lung adenocarcinoma proliferation and invasion by activating Wnt/β-catenin signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Mutation in Smek2 regulating hepatic glucose metabolism causes hypersarcosinemia and hyperhomocysteinemia in rats.Scientific reports · 2023Article
- The disruption of the CCDC6 - PP4 axis induces a BRCAness like phenotype and sensitivity to PARP inhibitors in high-grade serous ovarian carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Ppp4r3a deficiency leads to depression-like behaviors in mice by modulating the synthesis of synaptic proteins.Disease models & mechanisms · 2022Article
- Comprehensive analysis of PPPCs family reveals the clinical significance of PPP1CA and PPP4C in breast cancer.Bioengineered · 2022Article
- Role of CRTC2 in Metabolic Homeostasis: Key Regulator of Whole-Body Energy Metabolism?Diabetes & metabolism journal · 2020Review
- Functional roles of protein phosphatase 4 in multiple aspects of cellular physiology: a friend and a foe.BMB reports · 2020Review
- Low utilization of glucose in the liver causes diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats.PloS one · 2020Article
- A candidate gene analysis and GWAS for genes associated with maternal nondisjunction of chromosome 21.PLoS genetics · 2019Article
- A High-Resolution Proteomic Landscaping of Primary Human Dental Stem Cells: Identification of SHED- and PDLSC-Specific Biomarkers.International journal of molecular sciences · 2018Article
- A variant in PPP4R3A protects against alzheimer-related metabolic decline.Annals of neurology · 2017Article
- Hepatic Crtc2 controls whole body energy metabolism via a miR-34a-Fgf21 axis.Nature communications · 2017Article
- Smek promotes corticogenesis through regulating Mbd3's stability and Mbd3/NuRD complex recruitment to genes associated with neurogenesis.PLoS biology · 2017Article
- Deregulation of CRTCs in Aging and Age-Related Disease Risk.Trends in genetics : TIG · 2017Review
- Protein phosphatase 4 coordinates glial membrane recruitment and phagocytic clearance of degenerating axons in Drosophila.Cell death & disease · 2017Article
- PLATINUM SENSITIVE 2 LIKE impacts growth, root morphology, seed set, and stress responses.PloS one · 2017Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fasting promotes hepatic gluconeogenesis to maintain glucose homeostasis. The cAMP-response element binding protein (CREB)-regulated transcriptional coactivator 2 (CRTC2) is responsible for transcriptional activation of gluconeogenic genes and is critical for conveying the opposing hormonal signals of glucagon and insulin in the liver. Here, we show that suppressor of MEK null 1 (SMEK1) and SMEK2 [protein phosphatase 4 (PP4) regulatory subunits 3a and 3b, respectively] are directly involved in the regulation of hepatic glucose metabolism in mice. Expression of hepatic SMEK1/2 is up-regulated during fasting or in mouse models of insulin-resistant conditions in a Peroxisome Proliferator-Activated Receptor-gamma Coactivator 1α (PGC-1α)-dependent manner. Overexpression of SMEK promotes elevations in plasma glucose with increased hepatic gluconeogenic gene expression, whereas depletion of the SMEK proteins reduces hyperglycemia and enhances CRTC2 phosphorylation; the effect is blunted by S171A CRTC2, which is refractory to salt-inducible kinase (SIK)-dependent inhibition. Taken together, we would propose that mammalian SMEK/PP4C proteins are involved in the regulation of hepatic glucose metabolism through dephosphorylation of CRTC2.
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