ArticleThe Journal of biological chemistry2017
Guanine nucleotide exchange factor Epac2-dependent activation of the GTP-binding protein Rap2A mediates cAMP-dependent growth arrest in neuroendocrine cells.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- Selective Epac2 antagonist attenuates cerebral infarction induced by secondary brain injury in rats.Experimental and therapeutic medicine · 2025Article
- The guanine nucleotide exchange factor RapGEF2 is required for ERK-dependent immediate-early gene (Egr1) activation during fear memory formation.Cellular and molecular life sciences : CMLS · 2024Article
- ERK-dependent induction of the immediate-early gene Egr1 and the late gene Gpr50 contribute to two distinct phases of PACAP Gs-GPCR signaling for neuritogenesis.Journal of neuroendocrinology · 2022Article
- cAMP-Dependent Synaptic Plasticity at the Hippocampal Mossy Fiber Terminal.Frontiers in synaptic neuroscience · 2022Review
- Cyclic AMP-dependent activation of ERK via GLP-1 receptor signalling requires the neuroendocrine cell-specific guanine nucleotide exchanger NCS-RapGEF2.Journal of neuroendocrinology · 2021Article
- Cocaine-Dependent Acquisition of Locomotor Sensitization and Conditioned Place Preference Requires D1 Dopaminergic Signaling through a Cyclic AMP, NCS-Rapgef2, ERK, and Egr-1/Zif268 Pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Application of Machine Learning and Weighted Gene Co-expression Network Algorithm to Explore the Hub Genes in the Aging Brain.Frontiers in aging neuroscience · 2021Article
- Krüppel-Like Factors 9 and 13 Block Axon Growth by Transcriptional Repression of Key Components of the cAMP Signaling Pathway.Frontiers in molecular neuroscience · 2020Article
- Chromaffin Cells of the Adrenal Medulla: Physiology, Pharmacology, and Disease.Comprehensive Physiology · 2019Article
- Sodium current inhibition following stimulation of exchange protein directly activated by cyclic-3',5'-adenosine monophosphate (Epac) in murine skeletal muscle.Scientific reports · 2019Article
- Cyclic AMP-dependent protein kinase A and EPAC mediate VIP and secretin stimulation of PAK4 and activation of NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2019Article
- Effect of A549 neuroendocrine differentiation on cytotoxic immune response.Endocrine connections · 2018Article
- Inhibition of Epac2 Attenuates Neural Cell Apoptosis and Improves Neurological Deficits in a Rat Model of Traumatic Brain Injury.Frontiers in neuroscience · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
First messenger-dependent activation of MAP kinases in neuronal and endocrine cells is critical for cell differentiation and function and requires guanine nucleotide exchange factor (GEF)-mediated activation of downstream Ras family small GTPases, which ultimately lead to ERK, JNK, and p38 phosphorylation. Because there are numerous GEFs and also a host of Ras family small GTPases, it is important to know which specific GEF-small GTPase dyad functions in a given cellular process. Here we investigated the upstream activators and downstream effectors of signaling via the GEF Epac2 in the neuroendocrine NS-1 cell line. Three cAMP sensors, Epac2, PKA, and neuritogenic cAMP sensor-Rapgef2, mediate distinct cellular outputs: p38-dependent growth arrest, cAMP response element-binding protein-dependent cell survival, and ERK-dependent neuritogenesis, respectively, in these cells. Previously, we found that cAMP-induced growth arrest of PC12 and NS-1 cells requires Epac2-dependent activation of p38 MAP kinase, which posed the important question of how Epac2 engages p38 without simultaneously activating other MAP kinases in neuronal and endocrine cells. We now show that the small GTP-binding protein Rap2A is the obligate effector for, and GEF substrate of, Epac2 in mediating growth arrest through p38 activation in NS-1 cells. This new pathway is distinctly parcellated from the G protein-coupled receptor → G
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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.