| Results show that Epac1 binds to importin beta1 which prevents its accumulation in plasma membrane and, uncover a cAMP-independent function of Epac1 at the plasma membrane in the regulation of neurite outgrowth. | Epac1 interacts with importin β1 and controls neurite outgrowth independently of cAMP and Rap1.
Baameur F, Singhmar P, Zhou Y, Hancock JF, Cheng X, Heijnen CJ, Kavelaars A., Free PMC Article | 05/19/2018 |
| Data show that the Epac-Rap1 signaling axis is involved in triapine resistance. | Loss of phosphodiesterase 4D mediates acquired triapine resistance via Epac-Rap1-Integrin signaling.
Miklos W, Heffeter P, Pirker C, Hager S, Kowol CR, van Schoonhoven S, Stojanovic M, Keppler BK, Berger W., Free PMC Article | 03/10/2018 |
| This study indicates a novel role for Epac1 in PGE2-induced epithelial-to-mesenchymal transition and subsequent activation of beta-catenin | Epac1 links prostaglandin E2 to β-catenin-dependent transcription during epithelial-to-mesenchymal transition.
Jansen SR, Poppinga WJ, de Jager W, Lezoualc'h F, Cheng X, Wieland T, Yarwood SJ, Gosens R, Schmidt M., Free PMC Article | 02/3/2018 |
| EPAC1 and EPAC2 expression levels were significantly lower in bladder cancer tissue than in normal bladder tissue. In addition, bladder cancer cell lines showed reduced EPAC1 mRNA expression. Furthermore, EPAC1 overexpression in bladder cancer cell lines induced morphologic changes and markedly suppressed cell migration without affecting cell viability. | Overexpression of exchange protein directly activated by cAMP-1 (EPAC1) attenuates bladder cancer cell migration.
Ichikawa H, Itsumi M, Kajioka S, Maki T, Lee K, Tomita M, Yamaoka S. | 01/20/2018 |
| study suggests for the first time the mechanistic insights of mode of action of a primary cAMP-dependent sensor, Exchange protein activated by cAMP 1 (EPAC1), via its interaction with A-kinase anchoring protein 9 (AKAP9). | Role of exchange protein directly activated by cAMP (EPAC1) in breast cancer cell migration and apoptosis.
Kumar N, Gupta S, Dabral S, Singh S, Sehrawat S. | 12/23/2017 |
| We show that hematopoietic cell generation requires cAMP signaling through the Exchange proteins activated by cAMP (cAMP-Epac) axis..in hematopoietic progenitor and stem-like cells, cAMP induction mitigated oxidative stress, created a redox-state balance, and enhanced C-X-C chemokine receptor type 4 (CXCR4) expression, benefiting the maintenance of these primitive cells | Cyclic AMP Signaling through Epac Axis Modulates Human Hemogenic Endothelium and Enhances Hematopoietic Cell Generation.
Saxena S, Rönn RE, Guibentif C, Moraghebi R, Woods NB., Free PMC Article | 11/25/2017 |
| No significant association was observed between RAPGEF3 SNPs and the risk of Alzheimer's disease or neuropsychiatric inventory scores. | Anxiety and depression with neurogenesis defects in exchange protein directly activated by cAMP 2-deficient mice are ameliorated by a selective serotonin reuptake inhibitor, Prozac.
Zhou L, Ma SL, Yeung PK, Wong YH, Tsim KW, So KF, Lam LC, Chung SK., Free PMC Article | 11/11/2017 |
| This review focus is on the function of Epac in the heart. Accumulating evidence has revealed that both Epac1 and Epac2 play important roles in the structure and function of the heart under physiological and pathological conditions. [review] | The role of Epac in the heart.
Fujita T, Umemura M, Yokoyama U, Okumura S, Ishikawa Y., Free PMC Article | 09/2/2017 |
| This interaction is promoted by EPAC1 activation, triggering its translocation to the plasma membrane and binding to NHERF1. Our findings identify a new CFTR-interacting protein and demonstrate that cAMP activates CFTR through two different but complementary pathways - the well-known PKA-dependent channel gating pathway and a new mechanism regulating endocytosis that involves EPAC1. | EPAC1 activation by cAMP stabilizes CFTR at the membrane by promoting its interaction with NHERF1.
Lobo MJ, Amaral MD, Zaccolo M, Farinha CM. | 08/12/2017 |
| The contribution of EGFR, EPAC, and Ca(2+) in CDCA-induced activation of CFTR-dependent Cl(-) secretion. | Chenodeoxycholic acid requires activation of EGFR, EPAC, and Ca2+ to stimulate CFTR-dependent Cl- secretion in human colonic T84 cells.
Domingue JC, Ao M, Sarathy J, Rao MC. | 06/10/2017 |
| Microtubule stabilization was further suggested by the finding that ascorbate increased the amount of Epac1 bound to alpha-tubulin. | Intracellular ascorbate tightens the endothelial permeability barrier through Epac1 and the tubulin cytoskeleton.
Parker WH, Rhea EM, Qu ZC, Hecker MR, May JM., Free PMC Article | 06/10/2017 |
| during Epac1-induced activation of mTORC1 and mTORC2, Epac1 may have an additional function as a scaffold protein | Upregulation of mTORC2 activation by the selective agonist of EPAC, 8-CPT-2Me-cAMP, in prostate cancer cells: assembly of a multiprotein signaling complex.
Misra UK, Pizzo SV. | 05/27/2017 |
| The overexpression of EPAC1 can be used as a marker to predict the outcome of patients with GC, and EPAC1 represents a potential therapeutic modality for treating gastric cancer | EPAC1 overexpression is a prognostic marker and its inhibition shows promising therapeutic potential for gastric cancer.
Sun DP, Fang CL, Chen HK, Wen KS, Hseu YC, Hung ST, Uen YH, Lin KY., Free PMC Article | 04/22/2017 |
| our data provide new insight into the essential role of Epac1 in regulating growth of ovarian cancer cells and suggest that Epac1 might represent an attractive therapeutic target for treatment of ovarian cancer. | Epac1 knockdown inhibits the proliferation of ovarian cancer cells by inactivating AKT/Cyclin D1/CDK4 pathway in vitro and in vivo.
Gao M, Ma Y, Bast RC Jr, Li Y, Wan L, Liu Y, Sun Y, Fang Z, Zhang L, Wang X, Wei Z. | 04/22/2017 |
| These findings suggested Epac is connected to the SDF-1 signaling cascades. In conclusion, our study revealed that Epac plays a role in human mesenchymal stem cells (hMSCs)homing by promoting adhesion and migration. Appropriate manipulation of Epac may enhance the homing of hMSCs and facilitate their future clinical applications. | Epac Activation Regulates Human Mesenchymal Stem Cells Migration and Adhesion.
Yu JL, Deng R, Chung SK, Chan GC. | 01/14/2017 |
| EPAC activity is increased in arterial endothelial cells exposed to laminar-fluid shear stress, activation of EPAC1, and its activation of Rap1, plays a role in promoting alignment and elongation of these cells in the direction of flow. | EPAC1 promotes adaptive responses in human arterial endothelial cells subjected to low levels of laminar fluid shear stress: Implications in flow-related endothelial dysfunction.
Rampersad SN, Freitag SI, Hubert F, Brzezinska P, Butler N, Umana MB, Wudwud AR, Maurice DH. | 11/12/2016 |
| EPAC activation consistently reverses clinical and experimental impairment of neutrophil phagocytosis. EPAC signals through Rap-1 and bypasses RhoA. EPAC activation represents a novel potential means by which to reverse impaired neutrophil phagocytosis. | Exchange protein directly activated by cyclic AMP (EPAC) activation reverses neutrophil dysfunction induced by β2-agonists, corticosteroids, and critical illness.
Scott J, Harris GJ, Pinder EM, Macfarlane JG, Hellyer TP, Rostron AJ, Conway Morris A, Thickett DR, Perkins GD, McAuley DF, Widdrington JD, Wiscombe S, Baudouin SV, Roy AI, Linnett VC, Wright SE, Ruchaud-Sparagano MH, Simpson AJ. | 07/2/2016 |
| The cAMP exerted divergent effects on proliferation and promoted cell adhesion of different neuroendocrine cell types, these effects being mediated by both Epac and PKA and involving the same effector GTPase Rap1. | cAMP effects in neuroendocrine tumors: The role of Epac and PKA in cell proliferation and adhesion.
Vitali E, Cambiaghi V, Spada A, Tresoldi A, Zerbi A, Peverelli E, Carnaghi C, Mantovani G, Lania AG. | 05/28/2016 |
| Impaired microtubule dynamics, due to reduced EPAC1 signaling, links CFTR function to cystic fibrosis cellular events. | Role of Exchange Protein Activated by cAMP 1 in Regulating Rates of Microtubule Formation in Cystic Fibrosis Epithelial Cells.
Rymut SM, Ivy T, Corey DA, Cotton CU, Burgess JD, Kelley TJ., Free PMC Article | 04/9/2016 |
| Identified a conserved nuclear pore localisation signal (NPLS; amino acids 764-838 of EPAC1) in the catalytic domains of the cAMP-sensors, EPAC1 and EPAC2A. EPAC1 and EPAC2, display distinct subcellular distributions. | The cAMP sensors, EPAC1 and EPAC2, display distinct subcellular distributions despite sharing a common nuclear pore localisation signal.
Parnell E, Smith BO, Yarwood SJ., Free PMC Article | 12/19/2015 |
| Thyroid carcinoma cell lines showed no or very weak EPAC1 expression and exhibited no growth-promoting effect after EPAC stimulation. | Expression of the cAMP binding protein EPAC1 in thyroid tumors and growth regulation of thyroid cells and thyroid carcinoma cells by EPAC proteins.
Broecker-Preuss M, Baten J, Sheu-Grabellus SY, Görges R, Bockisch A, Schmid KW, Führer D, Mann K. | 12/19/2015 |
| findings, coupled with the development of EPAC specific small molecule modulators, validate EPAC1 as a promising target for therapeutic interventions | Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics.
Banerjee U, Cheng X., Free PMC Article | 11/21/2015 |
| association of ezrin with the actin cytoskeleton and phosphorylation on Thr567 are required, but not sufficient, for PKA and EPAC1 to synergistically promote cell spreading following elevations in intracellular cAMP. | Phosphorylation of ezrin on Thr567 is required for the synergistic activation of cell spreading by EPAC1 and protein kinase A in HEK293T cells.
Parnell E, Koschinski A, Zaccolo M, Cameron RT, Baillie GS, Baillie GL, Porter A, McElroy SP, Yarwood SJ., Free PMC Article | 08/29/2015 |
| These results demonstrate that glucagon increases hepatic FGF21 secretion via a posttranscriptional mechanism and provide evidence that both the PKA branch and EPAC branch of the cAMP pathway play a role in mediating this effect. | Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent posttranscriptional mechanism.
Cyphert HA, Alonge KM, Ippagunta SM, Hillgartner FB., Free PMC Article | 05/30/2015 |
| Sequestration of sperm Rab27 prevents subsequent cAMP/Epac-dependent calcium mobilization from the acrosome. | Epac, Rap and Rab3 act in concert to mobilize calcium from sperm's acrosome during exocytosis.
Ruete MC, Lucchesi O, Bustos MA, Tomes CN., Free PMC Article | 04/11/2015 |