ArticleMolecular pharmacology2013
Smoothened is a fully competent activator of the heterotrimeric G protein G(i).
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- Smoothened and ciliary GPCRs regulate ciliary protein kinase A activity involved in Hedgehog signal transduction.PLoS biology · 2026Article
- The GPCR Smoothened on cholinergic interneurons modulates dopamine-associated acetylcholine dynamics, learning, and effort management.iScience · 2026Article
- Hedgehog pathway activity downstream of Smoothened is regulated specifically by basal ciliary PKA.Cellular & molecular biology letters · 2026Article
- Essential strategies for the detection of constitutive and ligand-dependent Gi-directed activity of 7TM receptors using bioluminescence resonance energy transfer.bioRxiv : the preprint server for biology · 2024Article
- 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
- Article
- A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction.Nature structural & molecular biology · 2022Article
- TMED2 binding restricts SMO to the ER and Golgi compartments.PLoS biology · 2022Article
- Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium.Science China. Life sciences · 2022Review
- Hedgehog/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease.Cancers · 2021Review
- Residue 6.43 defines receptor function in class F GPCRs.Nature communications · 2021Article
- Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits.PLoS biology · 2021Article
- Ubiquitin-protein ligase Ubr5 cooperates with hedgehog signalling to promote skeletal tissue homeostasis.PLoS genetics · 2021Article
- Extensive crosstalk of G protein-coupled receptors with the Hedgehog signalling pathway.Development (Cambridge, England) · 2021Article
- Changes in Cellular Regulatory Factors before and after Decompression of Odontogenic Keratocysts.Journal of clinical medicine · 2020Article
- Range of SHH signaling in adrenal gland is limited by membrane contact to cells with primary cilia.The Journal of cell biology · 2020Article
- Low-density lipoprotein receptor-related protein 6-mediated signaling pathways and associated cardiovascular diseases: diagnostic and therapeutic opportunities.Human genetics · 2020Review
- Cannabinoids Exacerbate Alcohol Teratogenesis by a CB1-Hedgehog Interaction.Scientific reports · 2019Article
- Biochemical mechanisms of vertebrate hedgehog signaling.Development (Cambridge, England) · 2019Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Smoothened (Smo) is a 7-transmembrane protein essential to the activation of Gli transcription factors (Gli) by hedgehog morphogens. The structure of Smo implies interactions with heterotrimeric G proteins, but the degree to which G proteins participate in the actions of hedgehogs remains controversial. We posit that the G(i) family of G proteins provides to hedgehogs the ability to expand well beyond the bounds of Gli. In this regard, we evaluate here the efficacy of Smo as it relates to the activation of G(i), by comparing Smo with the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor, a quintessential G(i)-coupled receptor. We find that with use of [(35)S]guanosine 5'-(3-O-thio)triphosphate, first, with forms of G(i) endogenous to human embryonic kidney (HEK)-293 cells made to express epitope-tagged receptors and, second, with individual forms of Gα(i) fused to the C terminus of each receptor, Smo is equivalent to the 5-HT(1A) receptor in the assay as it relates to capacity to activate G(i). This finding is true regardless of subtype of G(i) (e.g., G(i2), G(o), and G(z)) tested. We also find that Smo endogenous to HEK-293 cells, ostensibly through inhibition of adenylyl cyclase, decreases intracellular levels of cAMP. The results indicate that Smo is a receptor that can engage not only Gli but also other more immediate effectors.
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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.