ArticleMolecular and cellular biology2008
Ras is required for the cyclic AMP-dependent activation of Rap1 via Epac2.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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
32 citing papers in PubMed, 60 citations in OpenAlex.
- Investigating the Effects of Epac2 Activation in an In Vitro Cortical Mechanical Injury Model for Central Nervous System Repair.The European journal of neuroscience · 2025Article
- Protein SUMOylation promotes cAMP-independent EPAC1 activation.Cellular and molecular life sciences : CMLS · 2024Article
- Review
- Article
- The Role of Epac in Cancer Progression.International journal of molecular sciences · 2020Review
- EPAC in Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020Review
- EPAC2: A new and promising protein for glioma pathogenesis and therapy.Oncology reviews · 2020Article
- Epidermal growth factor receptor controls glycogen phosphorylase in T cells through small GTPases of the RAS family.The Journal of biological chemistry · 2019Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Role of exchange protein directly activated by cAMP (EPAC1) in breast cancer cell migration and apoptosis.Molecular and cellular biochemistry · 2017Article
- Phosphorylation of Rap1 by cAMP-dependent Protein Kinase (PKA) Creates a Binding Site for KSR to Sustain ERK Activation by cAMP.The Journal of biological chemistry · 2017Article
- Protein Kinase A-independent Ras Protein Activation Cooperates with Rap1 Protein to Mediate Activation of the Extracellular Signal-regulated Kinases (ERK) by cAMP.The Journal of biological chemistry · 2016Article
- Activation of MEK/ERK Signaling by PACAP in Guinea Pig Cardiac Neurons.Journal of molecular neuroscience : MN · 2016Article
- Review
- Role of EPAC in cAMP-Mediated Actions in Adrenocortical Cells.Frontiers in endocrinology · 2016Review
- Allosteric inhibition of Epac: computational modeling and experimental validation to identify allosteric sites and inhibitors.The Journal of biological chemistry · 2014Article
- Identification and validation of modulators of exchange protein activated by cAMP (Epac) activity: structure-function implications for Epac activation and inhibition.The Journal of biological chemistry · 2014Article
- Protein kinase A-dependent phosphorylation of Rap1 regulates its membrane localization and cell migration.The Journal of biological chemistry · 2013Article
- Ras-mutant cancer cells display B-Raf binding to Ras that activates extracellular signal-regulated kinase and is inhibited by protein kinase A phosphorylation.The Journal of biological chemistry · 2013Article
- DNA methylation of alternative promoters directs tissue specific expression of Epac2 isoforms.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Exchange proteins activated by cAMP (cyclic AMP) 2 (Epac2) is a guanine nucleotide exchange factor for Rap1, a small G protein involved in many cellular functions, including cell adhesion, differentiation, and exocytosis. Epac2 interacts with Ras-GTP via a Ras association (RA) domain. Previous studies have suggested that the RA domain was dispensable for Epac2 function. Here we show for the first time that Ras and cAMP regulate Epac2 function in a parallel fashion and the Ras-Epac2 interaction is required for the cAMP-dependent activation of endogenous Rap1 by Epac2. The mechanism for this requirement is not allosteric activation of Epac2 by Ras but the compartmentalization of Epac2 on the Ras-containing membranes. A computational modeling is consistent with this compartmentalization being a function of both the level of Ras activation and the affinity between Ras and Epac2. In PC12 cells, a well-established model for sympathetic neurons, the Epac2 signaling is coupled to activation of mitogen-activated protein kinases and contributes to neurite outgrowth. Taken together, the evidence shows that Epac2 is not only a cAMP sensor but also a bona fide Ras effector. Coincident detection of both cAMP and Ras signals is essential for Epac2 to activate Rap1 in a temporally and spatially controlled manner.
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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.