ArticleCellular signalling2013
Interaction of PACAP with Sonic hedgehog reveals complex regulation of the hedgehog pathway by PKA.
Article in Cellular signalling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 63 citations in OpenAlex.
- Convergent mechanisms in Wnt and Hedgehog signaling.Science signaling · 2026Review
- Molecular signatures and lineage diversification of neurogenic and gliogenic radial glia in the gyrencephalic ferret cortex.Communications biology · 2026Article
- Molecular signatures and lineage diversification of neurogenic and gliogenic radial glia in the gyrencephalic ferret cortex.Research square · 2025Article
- Article
- The exocyst complex and intracellular vesicles mediate soluble protein trafficking to the primary cilium.Communications biology · 2024Article
- Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium.Science China. Life sciences · 2022Review
- Neuronal Polarity Pathways as Central Integrators of Cell-Extrinsic Information During Interactions of Neural Progenitors With Germinal Niches.Frontiers in molecular neuroscience · 2022Review
- Sonic Hedgehog Signaling in Cerebellar Development and Cancer.Frontiers in cell and developmental biology · 2022Review
- GPharmacological reviews · 2021Review
- Article
- Extensive crosstalk of G protein-coupled receptors with the Hedgehog signalling pathway.Development (Cambridge, England) · 2021Article
- Current knowledge of pituitary adenylate cyclase activating polypeptide (PACAP) in articular cartilage.Histology and histopathology · 2020Review
- Crosstalk of Hedgehog and mTORC1 Pathways.Cells · 2020Review
- Age-related alterations of articular cartilage in pituitary adenylate cyclase-activating polypeptide (PACAP) gene-deficient mice.GeroScience · 2019Article
- Biochemical mechanisms of vertebrate hedgehog signaling.Development (Cambridge, England) · 2019Review
- Differential Expression of Mitochondrial Biogenesis Markers in Mouse and Human SHH-Subtype Medulloblastoma.Cells · 2019Article
- Review
- Article
- Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Oxidative and Mechanical Stress-Evoked Matrix Degradation in Chondrifying Cell Cultures.International journal of molecular sciences · 2019Article
- Activation of Smoothened in the Hedgehog pathway unexpectedly increases GαThe Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule cell progenitors (cGCPs) and its aberrant activation causes a cerebellar cancer medulloblastoma. Pituitary adenylate cyclase activating polypeptide (PACAP) inhibits Shh-driven proliferation of cGCPs and acts as tumor suppressor in murine medulloblastoma. We show that PACAP blocks canonical Shh signaling by a mechanism that involves activation of protein kinase A (PKA) and inhibition of the translocation of the Shh-dependent transcription factor Gli2 into the primary cilium. PKA is shown to play an essential role in inhibiting gene transcription in the absence of Shh, but global PKA activity levels are found to be a poor predictor of the degree of Shh pathway activation. We propose that the core Shh pathway regulates a small compartmentalized pool of PKA in the vicinity of primary cilia. GPCRs that affect global PKA activity levels, such as the PACAP receptor, cooperate with the canonical Shh signal to regulate Gli protein phosphorylation by PKA. This interaction serves to fine-tune the transcriptional and physiological function of the Shh pathway.
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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.