ArticleProceedings of the National Academy of Sciences of the United States of America2016
MEKK2 mediates an alternative β-catenin pathway that promotes bone formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Structural basis for MEKK2 dimerization and substrate recognition.Nature communications · 2025Article
- MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitination.Experimental & molecular medicine · 2025Article
- Fufang Zhenshu Tiaozhi capsule enhances bone formation and safeguards against glucocorticoid-induced osteoporosis through innovative Mekk2-mediated β-catenin deubiquitination.Journal of bone and mineral metabolism · 2024Article
- USP36 regulates the proliferation, survival, and differentiation of hFOB1.19 osteoblast.Journal of orthopaedic surgery and research · 2024Article
- β-catenin inhibitors in cancer therapeutics: intricacies and way forward.Bioengineered · 2023Review
- Ubiquitin-specific peptidases: Players in bone metabolism.Cell proliferation · 2023Review
- Genome-wide screening for deubiquitinase subfamily identifies ubiquitin-specific protease 49 as a novel regulator of odontogenesis.Cell death and differentiation · 2022Article
- MiR-20a-5p facilitates cartilage repair in osteoarthritis via suppressing mitogen-activated protein kinase kinase kinase 2.Bioengineered · 2022Article
- The Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Pathway in Osteoblasts.Journal of bone metabolism · 2022Article
- Genome-Wide CRISPR/Cas9-Based Screening for Deubiquitinase Subfamily Identifies Ubiquitin-Specific Protease 11 as a Novel Regulator of Osteogenic Differentiation.International journal of molecular sciences · 2022Article
- Phosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling.Frontiers in oncology · 2022Review
- The Functional Role of Long Non-Coding RNAs in Melanoma.Cancers · 2021Review
- Expression and Role of Ubiquitin-Specific Peptidases in Osteoblasts.International journal of molecular sciences · 2021Review
- The Multifaceted Roles of USP15 in Signal Transduction.International journal of molecular sciences · 2021Review
- MAP3K2 augments Th1 cell differentiation via IL-18 to promote T cell-mediated colitis.Science China. Life sciences · 2021Article
- Deubiquitylases in developmental ubiquitin signaling and congenital diseases.Cell death and differentiation · 2021Review
- Downregulation of the Proton-Activated Cl- Channel TMEM206 Inhibits Malignant Properties of Human Osteosarcoma Cells.Oxidative medicine and cellular longevity · 2021Article
- CircPUM1 promotes hepatocellular carcinoma progression through the miR-1208/MAP3K2 axis.Journal of cellular and molecular medicine · 2021Article
- Adiponectin as Well as Compressive Forces RegulateFrontiers in cell and developmental biology · 2021Article
- MEKK2 mediates aberrant ERK activation in neurofibromatosis type I.Nature communications · 2020Article
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 4 countries.
Funding
Abstract
Proper tuning of β-catenin activity in osteoblasts is required for bone homeostasis, because both increased and decreased β-catenin activity have pathologic consequences. In the classical pathway for β-catenin activation, stimulation with WNT ligands suppresses constitutive phosphorylation of β-catenin by glycogen synthase kinase 3β, preventing β-catenin ubiquitination and proteasomal degradation. Here, we have found that mitogen-activated protein kinase kinase kinase 2 (MAP3K2 or MEKK2) mediates an alternative pathway for β-catenin activation in osteoblasts that is distinct from the canonical WNT pathway. FGF2 activates MEKK2 to phosphorylate β-catenin at serine 675, promoting recruitment of the deubiquitinating enzyme, ubiquitin-specific peptidase 15 (USP15). USP15 in turn prevents the basal turnover of β-catenin by inhibiting its ubiquitin-dependent proteasomal degradation, thereby enhancing WNT signaling. Analysis of MEKK2-deficient mice and genetic interaction studies between Mekk2- and β-catenin-null alleles confirm that this pathway is an important physiologic regulator of bone mass in vivo. Thus, an FGF2/MEKK2 pathway mediates an alternative nonclassical pathway for β-catenin activation, and this pathway is a key regulator of bone formation by osteoblasts.
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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.