ArticleThe Journal of biological chemistry2013
Smoothened oligomerization/higher order clustering in lipid rafts is essential for high Hedgehog activity transduction.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 56 citations in OpenAlex.
- Mevalonate pathway in pancreatic ductal adenocarcinoma: Mechanisms driving metabolic and cellular plasticity.Cancer pathogenesis and therapy · 2026Review
- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
- Cancer stem cell heterogeneity‑inspired therapeutics for enhancing tumor treatment outcomes (Review).International journal of oncology · 2026Review
- Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer.Journal of personalized medicine · 2022Review
- Article
- The lipid rafts in cancer stem cell: a target to eradicate cancer.Stem cell research & therapy · 2022Review
- Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review.Cellular and molecular life sciences : CMLS · 2022Review
- Smoothened (SMO) regulates insulin-like growth factor 1 receptor (IGF1R) levels and protein kinase B (AKT) localization and signaling.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR/Src/Erk/SP1 signaling-mediated ERRα re-expression.Molecular cancer · 2022Article
- Lipid raft involvement in signal transduction in cancer cell survival, cell death and metastasis.Cell proliferation · 2022Review
- A novel protein encoded by circular SMO RNA is essential for Hedgehog signaling activation and glioblastoma tumorigenicity.Genome biology · 2021Article
- Rafting Down the Metastatic Cascade: The Role of Lipid Rafts in Cancer Metastasis, Cell Death, and Clinical Outcomes.Cancer research · 2021Review
- A multiscale study on the mechanisms of spatial organization in ligand-receptor interactions on cell surfaces.Computational and structural biotechnology journal · 2021Article
- Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting.Scientific reports · 2020Article
- EGFR/ErbB Inhibition Promotes OPC Maturation up to Axon Engagement by Co-Regulating PIP2 and MBP.Cells · 2019Article
- TRAF3-interacting JNK-activating modulator promotes inflammation by stimulating translocation of Toll-like receptor 4 to lipid rafts.The Journal of biological chemistry · 2019Article
- PKAc-directed interaction and phosphorylation of Ptc is required for Hh signaling inhibition inCell discovery · 2019Article
- The mystery of membrane organization: composition, regulation and roles of lipid rafts.Nature reviews. Molecular cell biology · 2017Review
- Regulation of Smoothened Trafficking and Hedgehog Signaling by the SUMO Pathway.Developmental cell · 2016Article
- A positive role for polycomb in transcriptional regulation via H4K20me1.Cell research · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hedgehog (Hh) signaling pathway plays evolutionarily conserved roles in controlling embryonic development and tissue homeostasis, and its dysregulation has been implicated in many human diseases including congenital disorder and cancer. The Hh pathway has a unique signal reception system that includes two membrane proteins, the receptor Patched (Ptc) and the transducer Smoothened (Smo). In the Hh signaling cascade, Smo plays a critical role in controlling transduction of Hh gradient signal from the outside into the inside of cells. Although the Smo downstream signal transduction has been intensively studied, the mechanism by which Smo on the plasma membrane is regulated has not been fully understood. As a specific membrane structure of metazoan cells, lipid rafts act as a platform to regulate signal transduction by forming a nanoscale cluster through protein-protein or protein-lipid interactions. However, it remains largely unknown whether lipid rafts are also involved in the regulation of Hh signal transduction. Here, we show that Smo extracellular domain (N terminus) and transmembrane domains form oligomers/higher order clusters in response to Hh signal. Furthermore, we identify that lipid rafts on the plasma membrane are essential for high level activity of Smo during the Hh signal transduction. Finally, our observation suggests that oligomerization/higher order clustering of Smo C-terminal cytoplasmic tail (C-tail) is essential for the transduction of high level Hh signal. Collectively, our data support that in response to Hh gradient signals, Smo transduces high level Hh signal by forming oligomers/higher order clusters in the lipid rafts of cell plasma membrane.
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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.