ArticleThe Journal of biological chemistry2008
Endocytosis of the type III transforming growth factor-beta (TGF-beta) receptor through the clathrin-independent/lipid raft pathway regulates TGF-beta signaling and receptor down-regulation.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed.
- GLIS3 drives epithelial-mesenchymal transition and cancer stem-like traits in stomach adenocarcinoma via TGFBR3-Hedgehog signaling.Frontiers in oncology · 2026Article
- TGF-β superfamily co-receptors in cancer.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- ALK1 regulates the internalization of endoglin and the type III TGF-β receptor.Molecular biology of the cell · 2021Article
- Article
- TGF-β Signaling.Biomolecules · 2020Review
- Dually modified transmembrane proteoglycans in development and disease.Cytokine & growth factor reviews · 2018Review
- The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling.Pharmacological reviews · 2017Review
- Altering the Proteoglycan State of Transforming Growth Factor β Type III Receptor (TβRIII)/Betaglycan Modulates Canonical Wnt/β-Catenin Signaling.The Journal of biological chemistry · 2016Article
- TβRIII Expression in Human Breast Cancer Stroma and the Role of Soluble TβRIII in Breast Cancer Associated Fibroblasts.Cancers · 2016Article
- Signaling Receptors for TGF-β Family Members.Cold Spring Harbor perspectives in biology · 2016Review
- The emerging roles of β-arrestins in fibrotic diseases.Acta pharmacologica Sinica · 2015Review
- TβRIII independently binds type I and type II TGF-β receptors to inhibit TGF-β signaling.Molecular biology of the cell · 2015Article
- Targeting TGFβ signaling in subchondral bone and articular cartilage homeostasis.Trends in pharmacological sciences · 2014Review
- Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease.Molecular genetics and metabolism · 2014Article
- Article
- Ephrin-B2 controls PDGFRβ internalization and signaling.Genes & development · 2013Article
- Type III TGF-β receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma.The Journal of clinical investigation · 2013Article
- Expression and function of transforming growth factor-β isoforms and cognate receptors in the rat urinary bladder following cyclophosphamide-induced cystitis.American journal of physiology. Renal physiology · 2013Article
- Agonist-induced down-regulation of endogenous protein kinase c α through an endolysosomal mechanism.The Journal of biological chemistry · 2013Article
- Involvement of β-arrestins in cancer progression.Molecular biology reports · 2013Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Transforming growth factor-beta (TGF-beta) signals through three highly conserved cell surface receptors, the type III TGF-beta receptor (T beta RIII), the type II TGF-beta receptor (T beta RII), and the type I TGF-beta receptor (T beta RI) to regulate diverse cellular processes including cell proliferation, differentiation, migration, and apoptosis. Although T beta RI and T beta RII undergo ligand-independent endocytosis by both clathrin-mediated endocytosis, resulting in enhanced signaling, and clathrin-independent endocytosis, resulting in receptor degradation, the mechanism and function of T beta RIII endocytosis is poorly understood. T beta RIII is a heparan sulfate proteoglycan with a short cytoplasmic tail that functions as a TGF-beta superfamily co-receptor, contributing to TGF-beta signaling through mechanisms yet to be fully defined. We have reported previously that T beta RIII endocytosis, mediated by a novel interaction with beta arrestin-2, results in decreased TGF-beta signaling. Here we demonstrate that T beta RIII undergoes endocytosis in a ligand and glycosaminoglycan modification-independent and cytoplasmic domain-dependent manner, with the interaction of Thr-841 in the cytoplasmic domain of T beta RIII with beta-arrestin2 enhancing T beta RIII endocytosis. T beta RIII undergoes both clathrin-mediated and clathrin-independent endocytosis. Importantly, inhibition of the clathrin-independent, lipid raft pathway, but not of the clathrin-dependent pathway, results in decreased TGF-beta1 induced Smad2 and p38 phosphorylation, supporting a specific role for clathrin-independent endocytosis of T beta RIII in regulating both Smad-dependent and Smad-independent TGF-beta signaling.
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Registered trials
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