ArticleDevelopment (Cambridge, England)2011
The Hedgehog-induced Smoothened conformational switch assembles a signaling complex that activates Fused by promoting its dimerization and phosphorylation.
Article in Development (Cambridge, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- 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
- Ulk4 promotes Shh signaling by regulating Stk36 ciliary localization and Gli2 phosphorylation.eLife · 2023Article
- ULK4 and Fused/STK36 interact to mediate assembly of a motile flagellum.Molecular biology of the cell · 2023Article
- 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
- Article
- 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
- Regulation of Hedgehog Signal Transduction by Ubiquitination and Deubiquitination.International journal of molecular sciences · 2021Review
- Expression and purification of fused kinase from insect cells forSTAR protocols · 2021Article
- Article
- Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused.EMBO reports · 2020Article
- 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
- Preparation, characterization of silver phyto nanoparticles and their impact on growth potential ofSaudi journal of biological sciences · 2018Article
- The emerging roles of phosphatases in Hedgehog pathway.Cell communication and signaling : CCS · 2017Review
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Authors and funding
4 authors.
Funding
Abstract
Hedgehog (Hh) transduces signal by regulating the subcellular localization and conformational state of the GPCR-like protein Smoothened (Smo) but how Smo relays the signal to cytoplasmic signaling components remains poorly understood. Here, we show that Hh-induced Smo conformational change recruits Costal2 (Cos2)/Fused (Fu) and promotes Fu kinase domain dimerization. We find that induced dimerization through the Fu kinase domain activates Fu by inducing multi-site phosphorylation of its activation loop (AL) and phospho-mimetic mutations of AL activate the Hh pathway. Interestingly, we observe that graded Hh signals progressively increase Fu kinase domain dimerization and AL phosphorylation, suggesting that Hh activates Fu in a dose-dependent manner. Moreover, we find that activated Fu regulates Cubitus interruptus (Ci) by both promoting its transcriptional activator activity and inhibiting its proteolysis into a repressor form. We provide evidence that activated Fu exerts these regulations by interfering with the formation of Ci-Sufu and Ci-Cos2-kinase complexes that normally inhibit Ci activity and promote its processing. Taken together, our results suggest that Hh-induced Smo conformational change facilitates the assembly of active Smo-Cos2-Fu signaling complexes that promote Fu kinase domain dimerization, phosphorylation and activation, and that Fu regulates both the activator and repressor forms of Ci.
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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.