ArticleNature communications2016
Bimodal antagonism of PKA signalling by ARHGAP36.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- ARHGAP36 imposes a bifurcate activation of adherens junction and actomyosin to promote entosis.Cell death and differentiation · 2026Article
- Regulation of Translation by PKA Signaling Pathway.International journal of molecular sciences · 2026Review
- Article
- Dissection of Gαs and Hedgehog Signaling Cross-talk Reveals Therapeutic Opportunities to Target Hedgehog-Dependent Tumors.Cancer research · 2026Article
- Targeting the Neuro-Immune Axis in Next-Generation Oncology: Discovery and Validation of βOncology research · 2026Review
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Molecular and genetic characterization of sex-linked orange coat color in the domestic cat.Current biology : CB · 2025Article
- Common and divergent pathways in early stages of glutamate and tau-mediated toxicities in neurodegeneration.Experimental neurology · 2024Article
- Tripartite interactions of PKA catalytic subunit and C-terminal domains of cardiac CaBMC biology · 2024Article
- Genetic patterning in hippocampus of rat undergoing impaired spatial memory induced by long-term heat stress.Heliyon · 2024Article
- Enhancer hijacking at the ARHGAP36 locus is associated with connective tissue to bone transformation.Nature communications · 2023Article
- A PKA inhibitor motif within SMOOTHENED controls Hedgehog signal transduction.Nature structural & molecular biology · 2022Article
- Fixing the GAP: The role of RhoGAPs in cancer.European journal of cell biology · 2022Review
- Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium.Science China. Life sciences · 2022Review
- The TBC1D31/praja2 complex controls primary ciliogenesis through PKA-directed OFD1 ubiquitylation.The EMBO journal · 2021Article
- Striatal transcriptome changes linked to drug-induced repetitive behaviors.The European journal of neuroscience · 2021Article
- Structure-activity mapping of ARHGAP36 reveals regulatory roles for its GAP homology and C-terminal domains.PloS one · 2021Article
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Complex roles of cAMP-PKA-CREB signaling in cancer.Experimental hematology & oncology · 2020Review
- Dramatic neurological and biological effects by botulinum neurotoxin type A on SH-SY5Y neuroblastoma cells, beyond the blockade of neurotransmitter release.BMC pharmacology & toxicology · 2020Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinase A is a key mediator of cAMP signalling downstream of G-protein-coupled receptors, a signalling pathway conserved in all eukaryotes. cAMP binding to the regulatory subunits (PKAR) relieves their inhibition of the catalytic subunits (PKAC). Here we report that ARHGAP36 combines two distinct inhibitory mechanisms to antagonise PKA signalling. First, it blocks PKAC activity via a pseudosubstrate motif, akin to the mechanism employed by the protein kinase inhibitor proteins. Second, it targets PKAC for rapid ubiquitin-mediated lysosomal degradation, a pathway usually reserved for transmembrane receptors. ARHGAP36 thus dampens the sensitivity of cells to cAMP. We show that PKA inhibition by ARHGAP36 promotes derepression of the Hedgehog signalling pathway, thereby providing a simple rationale for the upregulation of ARHGAP36 in medulloblastoma. Our work reveals a new layer of PKA regulation that may play an important role in development and disease.
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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.