ArticlePLoS biology2016
PI(4)P Promotes Phosphorylation and Conformational Change of Smoothened through Interaction with Its C-terminal Tail.
Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 77 citations in OpenAlex.
- Trisomy 21 alters ciliary localization of Sonic Hedgehog signaling proteins.bioRxiv : the preprint server for biology · 2026Article
- The exocyst in ciliogenesis.Renal failure · 2025Review
- A Novel Variant in the Cyto-Tail ofMolecular syndromology · 2024Article
- Phosphatidic acid binding to Patched contributes to the inhibition of Smoothened and Hedgehog signaling inScience signaling · 2023Article
- Phosphoinositides in New Spaces.Cold Spring Harbor perspectives in biology · 2023Review
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- Review
- Molecular pathways of liver regeneration: A comprehensive review.World journal of hepatology · 2021Review
- Hedgehog signaling and Tre1 regulate actin dynamics through PI(4,5)PCell reports · 2021Article
- A PI4KIIIα protein complex is required for cell viability during Drosophila wing development.Developmental biology · 2020Article
- Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling.American journal of human genetics · 2020Article
- Cellular homeostasis in theMolecular biology of the cell · 2020Article
- The ciliary phosphatidylinositol phosphatase Inpp5e plays positive and negative regulatory roles in Shh signaling.Development (Cambridge, England) · 2020Article
- A Genetic Screen inG3 (Bethesda, Md.) · 2020Article
- Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß.Angewandte Chemie (International ed. in English) · 2019Review
- Article
- Proteostasis in the Hedgehog signaling pathway.Seminars in cell & developmental biology · 2019Review
- Phosphoinositides in the kidney.Journal of lipid research · 2019Review
- Sonic hedgehog signaling in epithelial tissue development.Regenerative medicine research · 2019Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In Hedgehog (Hh) signaling, binding of Hh to the Patched-Interference Hh (Ptc-Ihog) receptor complex relieves Ptc inhibition on Smoothened (Smo). A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation. In this study, we found that Hh elevates production of phosphatidylinositol 4-phosphate (PI(4)P). Increased levels of PI(4)P promote, whereas decreased levels of PI(4)P inhibit, Hh signaling activity. We further found that PI(4)P directly binds Smo through an arginine motif, which then triggers Smo phosphorylation and activation. Moreover, we identified the pleckstrin homology (PH) domain of G protein-coupled receptor kinase 2 (Gprk2) as an essential component for enriching PI(4)P and facilitating Smo activation. PI(4)P also binds mouse Smo (mSmo) and promotes its phosphorylation and ciliary accumulation. Finally, Hh treatment increases the interaction between Smo and PI(4)P but decreases the interaction between Ptc and PI(4)P, indicating that, in addition to promoting PI(4)P production, Hh regulates the pool of PI(4)P associated with Ptc and Smo.
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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.