ArticleThe Journal of biological chemistry2010
MTMR4 attenuates transforming growth factor beta (TGFbeta) signaling by dephosphorylating R-Smads in endosomes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis.Communications biology · 2021Pooled it
- Analysis of Circulating MicroRNAs in Patients with Diabetic Foot Ulcers and Lower Limb Amputation.International journal of molecular sciences · 2026Article
- The Myotubularin Related Proteins and the Untapped Interaction Potential of Their Disordered C-Terminal Regions.Proteins · 2025Article
- Hypoxia exposure blunts angiogenic signaling and upregulates the antioxidant system in endothelial cells derived from elephant seals.BMC biology · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The key role of miRNA in syndromic and sporadic forms of ascending aortic aneurysms as biomarkers and targets of novel therapeutic strategies.Frontiers in genetics · 2024Review
- Recent advances of myotubularin-related (MTMR) protein family in cardiovascular diseases.Frontiers in cardiovascular medicine · 2024Review
- TGFB1/INHBA Homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- MicroRNAs in ascending thoracic aortic aneurysms.Bioscience reports · 2020Observational
- TGF-β Signaling.Biomolecules · 2020Review
- The myotubularin MTMR4 regulates phagosomal phosphatidylinositol 3-phosphate turnover and phagocytosis.The Journal of biological chemistry · 2019Article
- Socioeconomic status and DNA methylation from birth through mid-childhood: a prospective study in Project Viva.Epigenomics · 2019Article
- Specificity, versatility, and control of TGF-β family signaling.Science signaling · 2019Review
- Bap180/Baf180 is required to maintain homeostasis of intestinal innate immune response in Drosophila and mice.Nature microbiology · 2017Article
- Posttranslational Regulation of Smads.Cold Spring Harbor perspectives in biology · 2016Review
- TGF-β Signaling from Receptors to Smads.Cold Spring Harbor perspectives in biology · 2016Review
- Defining the Protein-Protein Interaction Network of the Human Protein Tyrosine Phosphatase Family.Molecular & cellular proteomics : MCP · 2016Article
- Protein competition switches the function of COP9 from self-renewal to differentiation.Nature · 2014Article
- Crystallization and preliminary X-ray crystallographic analysis of the PH-GRAM domain of human MTMR4.Acta crystallographica. Section F, Structural biology communications · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homeostasis of Smad phosphorylation at its C-terminal SXS motif is essential for transforming growth factor beta (TGFbeta) signaling. Whereas it is known that TGFbeta signaling can be terminated by phosphatases, which dephosphorylate R-Smads in the nucleus, it is unclear whether there are any cytoplasmic phosphatase(s) that can attenuate R-Smad phosphorylation and nuclear translocation. Here we demonstrate that myotubularin-related protein 4 (MTMR4), a FYVE domain-containing dual-specificity protein phosphatase (DSP), attenuates TGFbeta signaling by reducing the phosphorylation level of R-Smads in early endosomes. Co-immunoprecipitation experiments showed that endogenous MTMR4 interacts with phosphorylated R-Smads, and that this interaction is correlated with dephosphorylation of R-Smads. Further analysis showed that overexpression of MTMR4 resulted in the sequestration of activated Smad3 in the early endosomes, thus reducing its nuclear translocation. However, both point mutations at the conserved catalytic site of the phosphatase (MTMR4-C407S) and small interference RNA of endogenous Mtmr4 expression led to sustained Smad3 activation. This work therefore suggests that MTMR4 plays an important role in preventing the overactivation of TGFbeta signaling by dephosphorylating activated R-Smads that have been trafficked to early endosomes.
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