ArticleEMBO reports2016
An essential role for Grk2 in Hedgehog signalling downstream of Smoothened.
Article in EMBO reports, 2016. 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
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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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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.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- 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
- Hedgehog pathway activity downstream of Smoothened is regulated specifically by basal ciliary PKA.Cellular & molecular biology letters · 2026Article
- Proximity based proteomics reveals Git1 as a regulator of Smoothened signaling.bioRxiv : the preprint server for biology · 2025Article
- A simple and scalable zebrafish model of Sonic hedgehog medulloblastoma.Cell reports · 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
- GRK2 in cardiovascular disease and its potential as a therapeutic target.Journal of molecular and cellular cardiology · 2022Review
- A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction.Nature structural & molecular biology · 2022Article
- Canonical Hedgehog Pathway and Noncanonical GLI Transcription Factor Activation in Cancer.Cells · 2022Review
- Therapeutic Applications of Physalins: Powerful Natural Weapons.Frontiers in pharmacology · 2022Review
- Smoothened transduces Hedgehog signals via activity-dependent sequestration of PKA catalytic subunits.PLoS biology · 2021Article
- Reduced Granule Cell Proliferation and Molecular Dysregulation in the Cerebellum of Lysosomal Acid Phosphatase 2 (ACP2) Mutant Mice.International journal of molecular sciences · 2021Article
- Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment.Acta pharmaceutica Sinica. B · 2021Review
- Research Progress on Regulating LncRNAs of Hepatocellular Carcinoma Stem Cells.OncoTargets and therapy · 2021Review
- A Membrane-Tethered Ubiquitination Pathway Regulates Hedgehog Signaling and Heart Development.Developmental cell · 2020Article
- Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling.EMBO molecular medicine · 2020Article
- GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis.Scientific reports · 2019Article
- Biochemical mechanisms of vertebrate hedgehog signaling.Development (Cambridge, England) · 2019Review
- Role of Protein Kinases in Hedgehog Pathway Control and Implications for Cancer Therapy.Cancers · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The G-protein-coupled receptor kinase 2 (adrbk2/GRK2) has been implicated in vertebrate Hedgehog (Hh) signalling based on the effects of its transient knock-down in mammalian cells and zebrafish embryos. Here, we show that the response to Hh signalling is effectively abolished in the absence of Grk2 activity. Zebrafish embryos lacking all Grk2 activity are refractory to both Sonic hedgehog (Shh) and oncogenic Smoothened (Smo) activity, but remain responsive to inhibition of cAMP-dependent protein kinase (PKA) activity. Mutation of the kinase domain abrogates the rescuing activity of grk2 mRNA, suggesting that Grk2 acts in a kinase-dependent manner to regulate the response to Hh. Previous studies have suggested that Grk2 potentiates Smo activity by phosphorylating its C-terminal tail (CTT). In the zebrafish embryo, however, phosphomimetic Smo does not display constitutive activity, whereas phospho-null mutants retain activity, implying phosphorylation is neither sufficient nor necessary for Smo function. Since Grk2 rescuing activity requires the integrity of domains essential for its interaction with GPCRs, we speculate that Grk2 may regulate Hh pathway activity by downregulation of a GPCR.
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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.