ArticleDevelopmental cell2011
Hedgehog activates fused through phosphorylation to elicit a full spectrum of pathway responses.
Article in Developmental cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Phosphorylation-induced SUMOylation promotes Ulk4 condensation at the ciliary tip to transduce Hedgehog signal.Journal of cell science · 2025Article
- Hedgehog-stimulated phosphorylation at multiple sites activates Ci by altering Ci-Ci interfaces without full Suppressor of Fused dissociation.PLoS biology · 2025Article
- Physiological analysis of the mechanism of Ci transcription factor activation through multiple Fused phosphorylation sites in Hedgehog signal transduction.bioRxiv : the preprint server for biology · 2025Article
- Morphogen-induced kinase condensates transduce Hh signal by allosterically activating Gli.Science advances · 2025Article
- Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk.Genes & diseases · 2024Review
- Ulk4 promotes Shh signaling by regulating Stk36 ciliary localization and Gli2 phosphorylation.eLife · 2023Article
- Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives.Cancer communications (London, England) · 2023Review
- Dose-dependent phosphorylation and activation of Hh pathway transcription factors.Life science alliance · 2022Article
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- Gli Phosphorylation Code in Hedgehog Signal Transduction.Frontiers in cell and developmental biology · 2022Review
- Ci/Gli Phosphorylation by the Fused/Ulk Family Kinases.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Expression and purification of fused kinase from insect cells forSTAR protocols · 2021Article
- Article
- Emerging role of tumor cell plasticity in modifying therapeutic response.Signal transduction and targeted therapy · 2020Review
- Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused.EMBO reports · 2020Article
- Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020Review
- Phosphorylation of Ci/Gli by Fused Family Kinases Promotes Hedgehog Signaling.Developmental cell · 2019Article
- Activation of Smoothened in the Hedgehog pathway unexpectedly increases GαThe Journal of biological chemistry · 2018Article
- Casein kinase 1ε and 1α as novel players in polycystic kidney disease and mechanistic targets for (R)-roscovitine and (S)-CR8.American journal of physiology. Renal physiology · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In flies and mammals, extracellular Hedgehog (Hh) molecules alter cell fates and proliferation by regulating the levels and activities of Ci/Gli family transcription factors. How Hh-induced activation of transmembrane Smoothened (Smo) proteins reverses Ci/Gli inhibition by Suppressor of Fused (SuFu) and kinesin family protein (Cos2/Kif7) binding partners is a major unanswered question. Here we show that the Fused (Fu) protein kinase is activated by Smo and Cos2 via Fu- and CK1-dependent phosphorylation. Activated Fu can recapitulate a full Hh response, stabilizing full-length Ci via Cos2 phosphorylation and activating full-length Ci by antagonizing Su(fu) and by other mechanisms. We propose that Smo/Cos2 interactions stimulate Fu autoactivation by concentrating Fu at the membrane. Autoactivation primes Fu for additional CK1-dependent phosphorylation, which further enhances kinase activity. In this model, Smo acts like many transmembrane receptors associated with cytoplasmic kinases, such that pathway activation is mediated by kinase oligomerization and trans-phosphorylation.
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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.