ArticleCell discovery2019
PKAc-directed interaction and phosphorylation of Ptc is required for Hh signaling inhibition in
Article in Cell discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 3 of them syntheses that pooled it.
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Who cites it
13 citing papers in PubMed, 3 syntheses or guidelines pooled it, 6 citations in OpenAlex.
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- Evening chronotype is associated with higher circulating pyruvate levels in adults.Frontiers in nutrition · 2026Article
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- Molecular mechanisms underlying the lifespan and healthspan benefits of dietary restriction across species.Frontiers in genetics · 2026Review
- Research progress on the role of AGC kinase family in bladder cancer.Discover oncology · 2025Review
- Mechanisms Underlying Muscle-Related Diseases and Aging: Insights into Pathophysiology and Therapeutic Strategies.Muscles (Basel, Switzerland) · 2025Review
- Phosphatidic acid binding to Patched contributes to the inhibition of Smoothened and Hedgehog signaling inScience signaling · 2023Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ptc is a gatekeeper to avoid abnormal Hh signaling activation, but the key regulators involved in Ptc-mediated inhibition remain largely unknown. Here, we identify PKAc as a key regulator required for Ptc inhibitory function. In the absence of Hh, PKAc physically interacts with Ptc and phosphorylates Ptc at Ser-1150 and -1183 residues. The presence of Hh unleashes PKAc from Ptc and activates Hh signaling. By combining both in vitro and in vivo functional assays, we demonstrate that such Ptc-PKAc interaction and Ptc phosphorylation are both important for Ptc inhibitory function. Interestingly, we further demonstrate that PKAc is subjected to palmitoylation, contributing to its kinase activity on plasma membrane. Based on those novel findings, we establish a working model on Ptc inhibitory function: In the absence of Hh, PKAc interacts with and phosphorylates Ptc to ensure its inhibitory function; and Hh presence releases PKAc from Ptc, resulting in Hh signaling activation.
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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.