ArticleDevelopmental biology2012
Hh-induced Smoothened conformational switch is mediated by differential phosphorylation at its C-terminal tail in a dose- and position-dependent manner.
Article in Developmental biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Phosphatidic acid binding to Patched contributes to the inhibition of Smoothened and Hedgehog signaling inScience signaling · 2023Article
- Dose-dependent phosphorylation and activation of Hh pathway transcription factors.Life science alliance · 2022Article
- Article
- Hedgehog signaling and its molecular perspective with cholesterol: a comprehensive review.Cellular and molecular life sciences : CMLS · 2022Review
- Characterization of Smoothened Phosphorylation and Activation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Regulation of Smoothened Trafficking and Abundance in Hedgehog Signaling.Frontiers in cell and developmental biology · 2022Review
- Cholesterol and Hedgehog Signaling: Mutual Regulation and Beyond.Frontiers in cell and developmental biology · 2022Review
- Review
- G-Protein Coupled Receptors (GPCRs) in Insects-A Potential Target for New Insecticide Development.Molecules (Basel, Switzerland) · 2021Review
- Extensive crosstalk of G protein-coupled receptors with the Hedgehog signalling pathway.Development (Cambridge, England) · 2021Article
- Hedgehog signaling promotes lipolysis in adipose tissue through directly regulating Bmm/ATGL lipase.Developmental biology · 2020Article
- Analysis on gene modular network reveals morphogen-directed development robustness inCell discovery · 2020Article
- Cell Adhesion-Mediated Actomyosin Assembly Regulates the Activity of Cubitus Interruptus for Hematopoietic Progenitor Maintenance inGenetics · 2019Article
- 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
- An intracellular activation of Smoothened that is independent of Hedgehog stimulation inJournal of cell science · 2018Article
- A cell based, high throughput assay for quantitative analysis of Hedgehog pathway activation using a Smoothened activation sensor.Scientific reports · 2017Article
- SUMO regulates the activity of Smoothened and Costal-2 in Drosophila Hedgehog signaling.Scientific reports · 2017Article
- CK1 in Developmental Signaling: Hedgehog and Wnt.Current topics in developmental biology · 2017Review
- Regulation of Smoothened Trafficking and Hedgehog Signaling by the SUMO Pathway.Developmental cell · 2016Article
- Regulation of Smoothened Phosphorylation and High-Level Hedgehog Signaling Activity by a Plasma Membrane Associated Kinase.PLoS biology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The activation of Smoothened (Smo) requires phosphorylation at three clusters of Serine residues in Drosophila Hedgehog (Hh) signaling. However, the mechanism by which phosphorylation promotes Smo conformational change and subsequently activates Smo in response to Hh gradient remains unclear. Here, we show that the conformational states of Smo are determined by not only the amount but also the position of the negative charges provided by phosphorylation. By using a Smo phospho-specific antibody, we demonstrate that Smo is differentially phosphorylated at three clusters of serine residues in response to levels of Hh activity. Mutating the first cluster, compared to mutating the other clusters, impairs Smo activity more severely, whereas mutating the last cluster prohibits C-terminus dimerization. In addition, phosphorylation of the membrane proximal cluster promotes phosphorylation of the distal cluster. We propose a zipper-lock model in which the gradual phosphorylation at these clusters induces a gradual conformational change in the Smo cytoplasmic tail, which promotes the interaction between Smo and Costal2 (Cos2). Moreover, we show that Hh regulates both PKA and CK1 phosphorylation of Smo. Thus, the differential phosphorylation of Smo mediates the thresholds of Hh activity.
Indexed as
Identifiers
What OpenQuestion holds
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.