ArticleScience signaling2014
Hedgehog induces formation of PKA-Smoothened complexes to promote Smoothened phosphorylation and pathway activation.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 51 citations in OpenAlex.
- Notch-hedgehog antagonism regulates stem cell niche formation through an E2-E3-E3 ubiquitin module.EMBO reports · 2026Article
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Hedgehog and Drosophila germ cell migration.Development (Cambridge, England) · 2025Review
- 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
- Proximity based proteomics reveals Git1 as a regulator of Smoothened signaling.bioRxiv : the preprint server for biology · 2025Article
- Phosphatidic acid binding to Patched contributes to the inhibition of Smoothened and Hedgehog signaling inScience signaling · 2023Article
- Paralog-specific TTC30 regulation of Sonic hedgehog signaling.Frontiers in molecular biosciences · 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
- Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium.Science China. Life sciences · 2022Review
- Cell-Based Assays for Smoothened Ubiquitination and Sumoylation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Characterization of Smoothened Phosphorylation and Activation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Gli Phosphorylation Code in Hedgehog Signal Transduction.Frontiers in cell and developmental biology · 2022Review
- Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling.Frontiers in cell and developmental biology · 2022Review
- Regulation of Hedgehog Signal Transduction by Ubiquitination and Deubiquitination.International journal of molecular sciences · 2021Review
- Review
- Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits.PLoS biology · 2021Article
- Sterols in an intramolecular channel of Smoothened mediate Hedgehog signaling.Nature chemical biology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Hedgehog (Hh) is a secreted glycoprotein that binds its receptor Patched to activate the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor-like protein Smoothened (Smo). In Drosophila, protein kinase A (PKA) phosphorylates and activates Smo in cells stimulated with Hh. In unstimulated cells, PKA phosphorylates and inhibits the transcription factor Cubitus interruptus (Ci). We found that in cells exposed to Hh, the catalytic subunit of PKA (PKAc) bound to the juxtamembrane region of the carboxyl terminus of Smo. PKA-mediated phosphorylation of Smo further enhanced its association with PKAc to form stable kinase-substrate complexes that promoted the PKA-mediated transphosphorylation of Smo dimers. We identified multiple basic residues in the carboxyl terminus of Smo that were required for interaction with PKAc, Smo phosphorylation, and Hh pathway activation. Hh induced a switch from the association of PKAc with a cytosolic complex of Ci and the kinesin-like protein Costal2 (Cos2) to a membrane-bound Smo-Cos2 complex. Thus, our study uncovers a previously uncharacterized mechanism for regulation of PKA activity and demonstrates that the signal-regulated formation of kinase-substrate complexes plays a central role in Hh signal transduction.
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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.