ArticleDevelopmental biology2008
The decoupling of Smoothened from Galphai proteins has little effect on Gli3 protein processing and Hedgehog-regulated chick neural tube patterning.
Article in Developmental biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Smoothened and ciliary GPCRs regulate ciliary protein kinase A activity involved in Hedgehog signal transduction.PLoS biology · 2026Article
- Structural mechanism for noncanonical GPCR signaling in the Hedgehog pathway.Nature structural & molecular biology · 2026Article
- GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade.PLoS biology · 2024Article
- Emerging mechanistic understanding of cilia function in cellular signalling.Nature reviews. Molecular cell biology · 2024Review
- A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction.Nature structural & molecular biology · 2022Article
- Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium.Science China. Life sciences · 2022Review
- Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits.PLoS biology · 2021Article
- Biochemical mechanisms of vertebrate hedgehog signaling.Development (Cambridge, England) · 2019Review
- Coupling of Smoothened to inhibitory G proteins reduces voltage-gated KThe Journal of biological chemistry · 2018Article
- Overlap in signaling between Smoothened and the α subunit of the heterotrimeric G protein G13.PloS one · 2018Article
- Contributions of Noncanonical Smoothened Signaling During Embryonic Development.Journal of developmental biology · 2017Article
- Heterotrimeric G protein signaling in polycystic kidney disease.Physiological genomics · 2016Review
- The G protein Gαs acts as a tumor suppressor in sonic hedgehog signaling-driven tumorigenesis.Cell cycle (Georgetown, Tex.) · 2016Review
- Smoothened Regulation: A Tale of Two Signals.Trends in pharmacological sciences · 2016Review
- The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels.The Journal of biological chemistry · 2015Article
- Ins and outs of GPCR signaling in primary cilia.EMBO reports · 2015Review
- Repurposing the antihelmintic mebendazole as a hedgehog inhibitor.Molecular cancer therapeutics · 2015Article
- G-protein-coupled receptors, Hedgehog signaling and primary cilia.Seminars in cell & developmental biology · 2014Review
- Canonical and non-canonical Hedgehog signalling and the control of metabolism.Seminars in cell & developmental biology · 2014Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The Hedgehog (Hh) signal is transmitted by two receptor molecules, Patched (Ptc) and Smoothened (Smo). Ptc suppresses Smo activity, while Hh binds Ptc and alleviates the suppression, which results in activation of Hh targets. Smo is a seven-transmembrane protein with a long carboxyl terminal tail. Vertebrate Smo has been previously shown to be coupled to Galpha(i) proteins, but the biological significance of the coupling in Hh signal transduction is not clear. Here we show that although inhibition of Galpha(i) protein activity appears to significantly reduce Hh pathway activity in Ptc(-/-) mouse embryonic fibroblasts and the NIH3T3-based Shh-light cells, it fails to derepress Shh- or a Smo-agonist-induced inhibition of Gli3 protein processing, a known in vivo indicator of Hh signaling activity. The inhibition of Galpha(i) protein activity also cannot block the Sonic Hedgehog (Shh)-dependent specification of neural progenitor cells in the neural tube. Consistent with these results, overexpression of a constitutively active Galpha(i) protein, Galpha(i2)QL, cannot ectopically specify the neural cell types in the spinal cord, whereas an active Smo, SmoM2, can. Thus, our results indicate that the Smo-induced Galpha(i) activity plays an insignificant role in the regulation of Gli3 processing and Shh-regulated neural tube patterning.
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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.