ArticleMolecular biology of the cell2005
Epac activation converts cAMP from a proliferative into a differentiation signal in PC12 cells.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed, 110 citations in OpenAlex.
- Roflumilast, a phosphodiesterase-4 (PDE4) inhibitor, induces respiratory frequency plasticity that is resistant to inflammation in neonatal rat in vitro preparations.Respiratory physiology & neurobiology · 2025Article
- Non-Susceptibility Gene Variants in Head and Neck Paragangliomas.International journal of molecular sciences · 2024Article
- Neonatal Cardiovascular-Progenitor-Cell-Derived Extracellular Vesicles Activate YAP1 in Adult Cardiac Progenitor Cells.International journal of molecular sciences · 2023Article
- Epac: new emerging cAMP-binding protein.BMB reports · 2021Review
- Review
- Epac2 Elevation Reverses Inhibition by Chondroitin Sulfate ProteoglycansThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Genome-Wide Mapping Defines a Role for C/EBPβ and c-Jun in Non-Canonical Cyclic AMP Signalling.Cells · 2019Article
- Roles of Cyclic AMP Response Element Binding Activation in the ERK1/2 and p38 MAPK Signalling Pathway in Central Nervous System, Cardiovascular System, Osteoclast Differentiation and Mucin and Cytokine Production.International journal of molecular sciences · 2019Review
- 1-Molecules (Basel, Switzerland) · 2019Article
- Vasoactive intestinal peptide increases apoptosis of hepatocellular carcinoma by inhibiting the cAMP/Bcl-xL pathway.Cancer science · 2019Article
- Molecular mechanism of panaxydol on promoting axonal growth in PC12 cells.Neural regeneration research · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Exchange proteins directly activated by cAMP (EPACs): Emerging therapeutic targets.Bioorganic & medicinal chemistry letters · 2017Review
- Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair.International journal of molecular sciences · 2017Review
- Epac1 interacts with importin β1 and controls neurite outgrowth independently of cAMP and Rap1.Scientific reports · 2016Article
- Review
- Urinary EGF Receptor Ligand Excretion in Patients with Autosomal Dominant Polycystic Kidney Disease and Response to Tolvaptan.Clinical journal of the American Society of Nephrology : CJASN · 2015Article
- Exchange Protein Directly Activated by cAMP (EPAC) Regulates Neuronal Polarization through Rap1B.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Neuroprotective role of prostaglandin PGE2 EP2 receptor in hemin-mediated toxicity.Neurotoxicology · 2015Article
- Role of guanine-nucleotide exchange factor Epac in renal physiology and pathophysiology.American journal of physiology. Renal physiology · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elevation of the intracellular cAMP concentration ([cAMP]i) regulates metabolism, cell proliferation, and differentiation and plays roles in memory formation and neoplastic growth. cAMP mediates its effects mainly through activation of protein kinase A (PKA) as well as Epac1 and Epac2, exchange factors activating the small GTPases Rap1 and Rap2. However, how cAMP utilizes these effectors to induce distinct biological responses is unknown. We here studied the specific roles of PKA and Epac in neuroendocrine PC12 cells. In these cells, elevation of [cAMP]i activates extracellular signal-regulated kinase (ERK) 1/2 and induces low-degree neurite outgrowth. The present study showed that specific stimulation of PKA triggered ERK1/2 activation that was considerably more transient than that observed upon simultaneous activation of both PKA and Epac. Unexpectedly, the PKA-specific cAMP analog induced cell proliferation rather than neurite outgrowth. The proliferative signaling pathway activated by the PKA-specific cAMP analog involved activation of the epidermal growth factor receptor and ERK1/2. Activation of Epac appeared to extend the duration of PKA-dependent ERK1/2 activation and converted cAMP from a proliferative into an anti-proliferative, neurite outgrowth-promoting signal. Thus, the present study showed that the outcome of cAMP signaling can depend heavily on the set of cAMP effectors activated.
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.