ArticleProceedings of the National Academy of Sciences of the United States of America2012
cAMP regulates DEP domain-mediated binding of the guanine nucleotide exchange factor Epac1 to phosphatidic acid at the plasma membrane.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 84 citations in OpenAlex.
- A putative novel protein, DEPDC1B, is overexpressed in oral cancer patients, and enhanced anchorage-independent growth in oral cancer cells that is mediated by Rac1 and ERK.Journal of biomedical science · 2014Trial
- Transcription Activation of DEPDC1B Upon EBF1 Loss Contributes to Cell Cycle Progression and Epithelial-Mesenchymal Transition in Colon Adenocarcinoma.Biochemical genetics · 2026Article
- DEPDC7 couples homologous chromosome segregation to asymmetric cytokinesis through recruiting ARP2/3 complex in oocyte meiosis.Cell communication and signaling : CCS · 2026Article
- A SUMO-interacting motif in the guanine nucleotide exchange factor EPAC1 is required for subcellular targeting and function.bioRxiv : the preprint server for biology · 2025Article
- Decreased CREB phosphorylation impairs embryonic retinal neurogenesis in thebioRxiv : the preprint server for biology · 2024Article
- Role of EPAC1 in chronic pain.Biochemistry and biophysics reports · 2024Review
- Lipid remodeling in acrosome exocytosis: unraveling key players in the human sperm.Frontiers in cell and developmental biology · 2024Review
- Membranes prime the RapGEF EPAC1 to transduce cAMP signaling.Nature communications · 2023Article
- DEPDC1B promotes colorectal cancer via facilitating cell proliferation and migration while inhibiting apoptosis.Cell cycle (Georgetown, Tex.) · 2023Article
- DEPDC1B promotes development of cholangiocarcinoma through enhancing the stability of CDK1 and regulating malignant phenotypes.Frontiers in oncology · 2022Article
- Integrative QTL mapping and selection signatures in Groningen White Headed cattle inferred from whole-genome sequences.PloS one · 2022Article
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- Analysis of Ras-effector interaction competition in large intestine and colorectal cancer context.Small GTPases · 2021Article
- The Ins and Outs of RAS Effector Complexes.Biomolecules · 2021Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
- Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling.International journal of molecular sciences · 2020Review
- New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein.International journal of molecular sciences · 2020Review
- The first DEP domain of the RhoGEF P-Rex1 autoinhibits activity and contributes to membrane binding.The Journal of biological chemistry · 2020Article
- Article
- Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epac1 is a cAMP-regulated guanine nucleotide exchange factor for the small G protein Rap. Upon cAMP binding, Epac1 undergoes a conformational change that results in its release from autoinhibition. In addition, cAMP induces the translocation of Epac1 from the cytosol to the plasma membrane. This relocalization of Epac1 is required for efficient activation of plasma membrane-located Rap and for cAMP-induced cell adhesion. This translocation requires the Dishevelled, Egl-10, Pleckstrin (DEP) domain, but the molecular entity that serves as the plasma membrane anchor and the possible mechanism of regulated binding remains elusive. Here we show that Epac1 binds directly to phosphatidic acid. Similar to the cAMP-induced Epac1 translocation, this binding is regulated by cAMP and requires the DEP domain. Furthermore, depletion of phosphatidic acid by inhibition of phospholipase D1 prevents cAMP-induced translocation of Epac1 as well as the subsequent activation of Rap at the plasma membrane. Finally, mutation of a single basic residue within a polybasic stretch of the DEP domain, which abolishes translocation, also prevents binding to phosphatidic acid. From these results we conclude that cAMP induces a conformational change in Epac1 that enables DEP domain-mediated binding to phosphatidic acid, resulting in the tethering of Epac1 at the plasma membrane and subsequent activation of Rap.
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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.