ArticleProceedings of the National Academy of Sciences of the United States of America2013
Phosphodiesterase-8A binds to and regulates Raf-1 kinase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 57 citations in OpenAlex.
- Absence of arrhythmogenic effects in cAMP subcellular compartments supports PDE8 as a target in atrial fibrillation.Journal of molecular and cellular cardiology plus · 2026Article
- Regulation of cAMP levels in osteocytes by mechano-sensitive focal adhesion kinase and phosphodiesterase 8A.iScience · 2026Article
- Conformational Dynamics and Allostery in the cAMP-Protein Kinase A Signalosome.Advances in experimental medicine and biology · 2026Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- PDE10A as a novel diagnostic and therapeutic target in cancer: insights and challenges.Frontiers in oncology · 2025Review
- Extreme-Phenotype Genome-Wide Association Analysis for Growth Traits in Spotted Sea Bass (Animals : an open access journal from MDPI · 2024Article
- Disruption of the pro-oncogenic c-RAF-PDE8A complex represents a differentiated approach to treating KRAS-c-RAF dependent PDAC.Scientific reports · 2024Article
- cAMP-phosphodiesterase 4D7 (PDE4D7) forms a cAMP signalosome complex with DHX9 and is implicated in prostate cancer progression.Molecular oncology · 2024Article
- Origin and functional diversification of PAS domain, a ubiquitous intracellular sensor.Science advances · 2023Article
- Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.Journal of molecular and cellular cardiology · 2022Article
- Treatment of Experimental Autoimmune Encephalomyelitis with an Inhibitor of Phosphodiesterase-8 (PDE8).Cells · 2022Article
- The cAMP-signaling cancers: Clinically-divergent disorders with a common central pathway.Frontiers in endocrinology · 2022Review
- The Role of PDE8 in T Cell Recruitment and Function in Inflammation.Frontiers in cell and developmental biology · 2021Review
- Article
- Proteomimetics of Natural Regulators of JAK-STAT Pathway: Novel Therapeutic Perspectives.Frontiers in molecular biosciences · 2021Review
- Cyclic adenosine monophosphate (cAMP) signaling in melanocyte pigmentation and melanomagenesis.Pigment cell & melanoma research · 2021Review
- Targeting B-Raf inhibitor resistant melanoma with novel cell penetrating peptide disrupters of PDE8A - C-Raf.BMC cancer · 2019Article
- FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system.Molecular psychiatry · 2018Article
- PDE8 Is Expressed in Human Airway Smooth Muscle and Selectively Regulates cAMP Signaling by βAmerican journal of respiratory cell and molecular biology · 2018Article
Corrections and comments
- Commented on by
Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) is a key activator of the ERK pathway and is a target for cross-regulation of this pathway by the cAMP signaling system. The cAMP-activated protein kinase, PKA, inhibits Raf-1 by phosphorylation on S259. Here, we show that the cAMP-degrading phosphodiesterase-8A (PDE8A) associates with Raf-1 to protect it from inhibitory phosphorylation by PKA, thereby enhancing Raf-1's ability to stimulate ERK signaling. PDE8A binds to Raf-1 with high (picomolar) affinity. Mapping of the interaction domain on PDE8A using peptide array technology identified amino acids 454-465 as the main binding site, which could be disrupted by mutation. A cell-permeable peptide corresponding to this region disrupted the PDE8A/Raf-1 interaction in cells, thereby reducing ERK activation and the cellular response to EGF. Overexpression of a catalytically inactive PDE8A in cells displayed a dominant negative phenotype on ERK activation. These effects were recapitulated at the organism level in genetically modified (PDE8A(-/-)) mice. Similarly, PDE8 deletion in Drosophila melanogaster reduced basal ERK activation and sensitized flies to stress-induced death. We propose that PDE8A is a physiological regulator of Raf-1 signaling in some cells.
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.