RAPGEF3

Summary

Gene Symbol: RAPGEF3
Description: Rap guanine nucleotide exchange factor 3
Alias: CAMP-GEFI, EPAC, EPAC1, HSU79275, bcm910, rap guanine nucleotide exchange factor 3, 9330170P05Rik, EPAC 1, Rap guanine nucleotide exchange factor (GEF) 3, Rap1 guanine-nucleotide-exchange factor directly activated by cAMP, cAMP-regulated guanine nucleotide exchange factor I, exchange factor directly activated by cAMP 1, exchange protein directly activated by cAMP 1
Species: human
Products:     RAPGEF3

Top Publications

  1. de Rooij J, Zwartkruis F, Verheijen M, Cool R, Nijman S, Wittinghofer A, et al. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature. 1998;396:474-7 pubmed
    ..We have cloned the gene encoding a guanine-nucleotide-exchange factor (GEF) which we have named Epac (exchange protein directly activated by cAMP)...
  2. Lorenz R, Aleksic T, Wagner M, Adler G, Weber C. The cAMP/Epac1/Rap1 pathway in pancreatic carcinoma. Pancreas. 2008;37:102-3 pubmed publisher
  3. Sands W, Woolson H, Milne G, Rutherford C, Palmer T. Exchange protein activated by cyclic AMP (Epac)-mediated induction of suppressor of cytokine signaling 3 (SOCS-3) in vascular endothelial cells. Mol Cell Biol. 2006;26:6333-46 pubmed
    ..Consistent with this hypothesis, small interfering RNA-mediated knockdown of Epac1 was sufficient to attenuate both cAMP-mediated SOCS-3 induction and inhibition of STAT phosphorylation, suggesting ..
  4. Mei F, Cheng X. Interplay between exchange protein directly activated by cAMP (Epac) and microtubule cytoskeleton. Mol Biosyst. 2005;1:325-31 pubmed
    quot;Exchange protein directly activated by cAMP" (Epac) is a newly discovered cAMP receptor that mediates the intracellular cAMP actions in addition to the classic cAMP-dependent protein kinase system...
  5. Cullere X, Shaw S, Andersson L, Hirahashi J, Luscinskas F, Mayadas T. Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase. Blood. 2005;105:1950-5 pubmed
    ..Activation of a cAMP-inducible guanine-exchange factor for Rap, Epac, results in markedly enhanced basal endothelial barrier function by increasing cortical actin and subsequent ..
  6. Hochbaum D, Tanos T, Ribeiro Neto F, Altschuler D, Coso O. Activation of JNK by Epac is independent of its activity as a Rap guanine nucleotide exchanger. J Biol Chem. 2003;278:33738-46 pubmed
    ..Searching for novel regulators of JNK activity we have identified Epac (exchange protein activated by cAMP) as a strong activator of JNK-1...
  7. Kassel K, Wyatt T, Panettieri R, Toews M. Inhibition of human airway smooth muscle cell proliferation by beta 2-adrenergic receptors and cAMP is PKA independent: evidence for EPAC involvement. Am J Physiol Lung Cell Mol Physiol. 2008;294:L131-8 pubmed
    ..activated PKA (10-100 microM), whereas a cAMP analog selective for the exchange protein directly activated by cAMP (EPAC), 8-(4-chlorophenylthio)-2'-O-methyl-cAMP, maximally inhibited proliferation at a concentration that did not ..
  8. Kojima F, Kapoor M, Kawai S, Yang L, Aronoff D, Crofford L. Prostaglandin E2 activates Rap1 via EP2/EP4 receptors and cAMP-signaling in rheumatoid synovial fibroblasts: involvement of Epac1 and PKA. Prostaglandins Other Lipid Mediat. 2009;89:26-33 pubmed publisher
    ..RSF expressed the downstream signaling partners of cAMP, exchange protein directly activated by cAMP (Epac1) and protein kinase A (PKA)...
  9. López de Jesús M, Stope M, Oude Weernink P, Mahlke Y, Börgermann C, Ananaba V, et al. Cyclic AMP-dependent and Epac-mediated activation of R-Ras by G protein-coupled receptors leads to phospholipase D stimulation. J Biol Chem. 2006;281:21837-47 pubmed
    ..The receptor actions were mimicked by an Epac-specific cyclic AMP analog and suppressed by depletion of endogenous Epac1 by small interfering RNAs, as well as expression of a cyclic AMP binding-deficient Epac1 mutant, but not by ..

More Information

Publications83

  1. Fukuhara S, Sakurai A, Sano H, Yamagishi A, Somekawa S, Takakura N, et al. Cyclic AMP potentiates vascular endothelial cadherin-mediated cell-cell contact to enhance endothelial barrier function through an Epac-Rap1 signaling pathway. Mol Cell Biol. 2005;25:136-46 pubmed
    ..were mimicked by 8-(4-chlorophenylthio)-2'-O-methyladenosine-3', 5'-cyclic monophosphate, a specific activator for Epac, which is a novel cAMP-dependent guanine nucleotide exchange factor for Rap1...
  2. Liu C, Takahashi M, Li Y, Dillon T, Kaech S, Stork P. The interaction of Epac1 and Ran promotes Rap1 activation at the nuclear envelope. Mol Cell Biol. 2010;30:3956-69 pubmed publisher
    b>Epac1 (exchange protein directly activated by cyclic AMP [cAMP]) couples intracellular cAMP to the activation of Rap1, a Ras family GTPase that regulates cell adhesion, proliferation, and differentiation...
  3. Rehmann H, Prakash B, Wolf E, Rueppel A, de Rooij J, Bos J, et al. Structure and regulation of the cAMP-binding domains of Epac2. Nat Struct Biol. 2003;10:26-32 pubmed
    ..We identify a hinge region that couples cAMP binding to a conformational change of the C-terminal regions. Mutations in the hinge of Epac can uncouple cAMP binding from its exchange activity.
  4. Sehrawat S, Cullere X, Patel S, Italiano J, Mayadas T. Role of Epac1, an exchange factor for Rap GTPases, in endothelial microtubule dynamics and barrier function. Mol Biol Cell. 2008;19:1261-70 pubmed publisher
    ..Here, Epac1 was shown to be responsible for these actin changes and to colocalize with microtubules in human umbilical vein ..
  5. Ster J, de Bock F, Guerineau N, Janossy A, Barrère Lemaire S, Bos J, et al. Exchange protein activated by cAMP (Epac) mediates cAMP activation of p38 MAPK and modulation of Ca2+-dependent K+ channels in cerebellar neurons. Proc Natl Acad Sci U S A. 2007;104:2519-24 pubmed
    The exchange factor directly activated by cAMP (Epac) is a newly discovered direct target for cAMP and a guanine-nucleotide exchange factor for the small GTPase Rap. Little is known about the neuronal functions of Epac...
  6. Misra U, Pizzo S. Upregulation of mTORC2 activation by the selective agonist of EPAC, 8-CPT-2Me-cAMP, in prostate cancer cells: assembly of a multiprotein signaling complex. J Cell Biochem. 2012;113:1488-500 pubmed publisher
    ..Here we show in 1-LN prostate cancer cells that 8-CPT-2Me-cAMP causes a dose-dependent increase in Epac1, p-Akt(T308) , p-Akt(S473) , but not p-CREB...
  7. Kooistra M, Corada M, Dejana E, Bos J. Epac1 regulates integrity of endothelial cell junctions through VE-cadherin. FEBS Lett. 2005;579:4966-72 pubmed
    We have previously shown that Rap1 as well as its guanine nucleotide exchange factor Epac1 increases cell-cell junction formation...
  8. Baljinnyam E, Iwatsubo K, Kurotani R, Wang X, Ulucan C, Iwatsubo M, et al. Epac increases melanoma cell migration by a heparan sulfate-related mechanism. Am J Physiol Cell Physiol. 2009;297:C802-13 pubmed publisher
    ..It was recently demonstrated that Epac, an effector molecule of cAMP, is involved in regulating cell migration; however, the role of Epac in melanoma cell ..
  9. Baljinnyam E, Umemura M, De Lorenzo M, Iwatsubo M, Chen S, Goydos J, et al. Epac1 promotes melanoma metastasis via modification of heparan sulfate. Pigment Cell Melanoma Res. 2011;24:680-7 pubmed publisher
    ..In order to obtain conclusive evidence that Epac1 plays a critical role in modification of HS and melanoma metastasis, we extensively investigated expression and ..
  10. Fang Y, Olah M. Cyclic AMP-dependent, protein kinase A-independent activation of extracellular signal-regulated kinase 1/2 following adenosine receptor stimulation in human umbilical vein endothelial cells: role of exchange protein activated by cAMP 1 (Epac1). J Pharmacol Exp Ther. 2007;322:1189-200 pubmed
    ..Reverse Transcription-polymerase chain reaction analysis detected Epac1 but not Epac2 in HUVEC...
  11. Rampersad S, Ovens J, Huston E, Umana M, Wilson L, Netherton S, et al. Cyclic AMP phosphodiesterase 4D (PDE4D) Tethers EPAC1 in a vascular endothelial cadherin (VE-Cad)-based signaling complex and controls cAMP-mediated vascular permeability. J Biol Chem. 2010;285:33614-22 pubmed publisher
    ..Thus, we report that PKA, EPAC1, and cyclic nucleotide phosphodiesterase 4D (PDE4D) enzymes integrate into VE-Cad-based signaling complexes in ..
  12. de Rooij J, Rehmann H, van Triest M, Cool R, Wittinghofer A, Bos J. Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs. J Biol Chem. 2000;275:20829-36 pubmed
    b>Epac1 (cAMP-GEFI) and Epac2 (cAMP-GEFII) are closely related guanine nucleotide exchange factors (GEFs) for the small GTPase Rap1, which are directly regulated by cAMP. Here we show that both GEFs efficiently activate Rap2 as well...
  13. Dodge Kafka K, Soughayer J, Pare G, Carlisle Michel J, Langeberg L, Kapiloff M, et al. The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways. Nature. 2005;437:574-8 pubmed
    ..complex maintained by the muscle-specific A-kinase anchoring protein (mAKAP) that includes PKA, PDE4D3 and Epac1. These intermolecular interactions facilitate the dissemination of distinct cAMP signals through each effector ..
  14. Kawasaki H, Springett G, Mochizuki N, Toki S, Nakaya M, Matsuda M, et al. A family of cAMP-binding proteins that directly activate Rap1. Science. 1998;282:2275-9 pubmed
    ..Our findings suggest the need to reformulate concepts of cAMP-mediated signaling to include direct coupling to Ras superfamily signaling. ..
  15. Pereira L, Métrich M, Fernandez Velasco M, Lucas A, Leroy J, Perrier R, et al. The cAMP binding protein Epac modulates Ca2+ sparks by a Ca2+/calmodulin kinase signalling pathway in rat cardiac myocytes. J Physiol. 2007;583:685-94 pubmed
    ..The identification of a cAMP binding protein, Epac, raises the question of its role in Ca(2+) signalling in cardiac myocytes...
  16. Lorenowicz M, van Gils J, de Boer M, Hordijk P, Fernandez Borja M. Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis. J Leukoc Biol. 2006;80:1542-52 pubmed
    ..We investigated the role of a guanine nucleotide exchange protein for Rap1 directly activated by cAMP (Epac1) in adhesion and chemotaxis in a promonocytic cell line and in primary monocytes...
  17. Gloerich M, Ponsioen B, Vliem M, Zhang Z, Zhao J, Kooistra M, et al. Spatial regulation of cyclic AMP-Epac1 signaling in cell adhesion by ERM proteins. Mol Cell Biol. 2010;30:5421-31 pubmed publisher
    b>Epac1 is a guanine nucleotide exchange factor for the small G protein Rap and is involved in membrane-localized processes such as integrin-mediated cell adhesion and cell-cell junction formation...
  18. Mei F, Qiao J, Tsygankova O, Meinkoth J, Quilliam L, Cheng X. Differential signaling of cyclic AMP: opposing effects of exchange protein directly activated by cyclic AMP and cAMP-dependent protein kinase on protein kinase B activation. J Biol Chem. 2002;277:11497-504 pubmed
    The recent discovery of Epac, a novel cAMP receptor protein, opens up a new dimension in studying cAMP-mediated cell signaling...
  19. Ponsioen B, Gloerich M, Ritsma L, Rehmann H, Bos J, Jalink K. Direct spatial control of Epac1 by cyclic AMP. Mol Cell Biol. 2009;29:2521-31 pubmed publisher
    b>Epac1 is a guanine nucleotide exchange factor (GEF) for the small G protein Rap and is directly activated by cyclic AMP (cAMP)...
  20. Misra U, Pizzo S. Epac1-induced cellular proliferation in prostate cancer cells is mediated by B-Raf/ERK and mTOR signaling cascades. J Cell Biochem. 2009;108:998-1011 pubmed publisher
    cAMP-dependent, PKA-independent effects on cell proliferation are mediated by cAMP binding to EPAC and activation of Rap signaling...
  21. Gloerich M, Vliem M, Prummel E, Meijer L, Rensen M, Rehmann H, et al. The nucleoporin RanBP2 tethers the cAMP effector Epac1 and inhibits its catalytic activity. J Cell Biol. 2011;193:1009-20 pubmed publisher
    ..we demonstrate that the nuclear pore component RanBP2 acts as a negative regulator of cAMP signaling through Epac1, a cAMP-regulated guanine nucleotide exchange factor for Rap...
  22. Qiao J, Mei F, Popov V, Vergara L, Cheng X. Cell cycle-dependent subcellular localization of exchange factor directly activated by cAMP. J Biol Chem. 2002;277:26581-6 pubmed
    b>Epac belongs to a new family of proteins that can directly mediate the action of the intracellular second messenger cAMP by activating a downstream small GTPase Rap1...
  23. Yokoyama U, Patel H, Lai N, Aroonsakool N, Roth D, Insel P. The cyclic AMP effector Epac integrates pro- and anti-fibrotic signals. Proc Natl Acad Sci U S A. 2008;105:6386-91 pubmed publisher
    ..transforming growth factor beta1, transcriptionally decreases expression of Exchange protein activated by cAMP 1 (Epac1) in fibroblasts/fibroblast-like cells from multiple tissues (i.e...
  24. Kang G, Leech C, Chepurny O, Coetzee W, Holz G. Role of the cAMP sensor Epac as a determinant of KATP channel ATP sensitivity in human pancreatic beta-cells and rat INS-1 cells. J Physiol. 2008;586:1307-19 pubmed publisher
    Protein kinase A (PKA)-independent actions of adenosine 3',5'-cyclic monophosphate (cAMP) are mediated by Epac, a cAMP sensor expressed in pancreatic beta-cells...
  25. Kawasaki H, Springett G, Toki S, Canales J, Harlan P, Blumenstiel J, et al. A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia. Proc Natl Acad Sci U S A. 1998;95:13278-83 pubmed
    ..The expression of CalDAG-GEFI and CalDAG-GEFII in hematopoietic organs suggests that such control may have broad significance in Ras/Rap regulation of normal and malignant states. ..
  26. Huston E, Lynch M, Mohamed A, Collins D, Hill E, MacLeod R, et al. EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation. Proc Natl Acad Sci U S A. 2008;105:12791-6 pubmed publisher
    ..signaling system that identifies a functional role for the GTP exchange factor, exchange protein activated by cAMP (EPAC) coupled to Rap2 in the nucleus...
  27. Métrich M, Lucas A, Gastineau M, Samuel J, Heymes C, Morel E, et al. Epac mediates beta-adrenergic receptor-induced cardiomyocyte hypertrophy. Circ Res. 2008;102:959-65 pubmed publisher
    ..Here, we show that cardiac hypertrophy induced by thoracic aortic constriction increases Epac1 expression in rat myocardium...
  28. Grandoch M, Rose A, Ter Braak M, Jendrossek V, Rubben H, Fischer J, et al. Epac inhibits migration and proliferation of human prostate carcinoma cells. Br J Cancer. 2009;101:2038-42 pubmed publisher
    It was recently found that cAMP mediates protein kinase A-independent effects through Epac proteins. The aim of this study was to investigate the role of Epac in migration and proliferation of prostate carcinoma cells...
  29. Tiwari S, Felekkis K, Moon E, Flies A, Sherr D, Lerner A. Among circulating hematopoietic cells, B-CLL uniquely expresses functional EPAC1, but EPAC1-mediated Rap1 activation does not account for PDE4 inhibitor-induced apoptosis. Blood. 2004;103:2661-7 pubmed
    ..B-CLL and peripheral blood B cells express EPAC1 transcript, whereas T-CLL, peripheral blood T cells, monocytes, and neutrophils do not...
  30. Price L, Hajdo Milasinovic A, Zhao J, Zwartkruis F, Collard J, Bos J. Rap1 regulates E-cadherin-mediated cell-cell adhesion. J Biol Chem. 2004;279:35127-32 pubmed
    ..Activation of endogenous Rap via the Rap exchange factor Epac1 also antagonized hepatocyte growth factor-induced disruption of adherens junctions...
  31. Yang H, Vainshtein A, Maik Rachline G, Peles E. G protein-coupled receptor 37 is a negative regulator of oligodendrocyte differentiation and myelination. Nat Commun. 2016;7:10884 pubmed publisher
    ..of oligodendrocyte differentiation by GPR37 is mediated by suppression of an exchange protein activated by cAMP (EPAC)-dependent activation of Raf-MAPK-ERK1/2 module and nuclear translocation of ERK1/2...
  32. Köröskényi K, Kiss B, Szondy Z. Adenosine A2A receptor signaling attenuates LPS-induced pro-inflammatory cytokine formation of mouse macrophages by inducing the expression of DUSP1. Biochim Biophys Acta. 2016;1863:1461-71 pubmed publisher
    ..signaling inhibits LPS-induced pro-inflammatory cytokine production through a unique cAMP-dependent, but PKA- and Epac-independent signaling pathway. However, the mechanism of inhibition was not identified so far...
  33. Goupil S, Maréchal L, El Hajj H, Tremblay M, Richard F, Leclerc P. Identification and Localization of the Cyclic Nucleotide Phosphodiesterase 10A in Bovine Testis and Mature Spermatozoa. PLoS ONE. 2016;11:e0161035 pubmed publisher
    ..act through protein phosphorylation via PRKA and through the activation of guanine nucleotide exchange factors like EPAC. Sperm intracellular cAMP levels depend on the activity of adenylyl cyclases, mostly SACY, though transmembrane-..
  34. Cyphert H, Alonge K, Ippagunta S, Hillgartner F. Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent posttranscriptional mechanism. PLoS ONE. 2014;9:e94996 pubmed publisher
    ..Incubating hepatocytes with an exchange protein directly activated by cAMP (EPAC)-selective cAMP analog [i.e...
  35. Sugawara K, Shibasaki T, Takahashi H, Seino S. Structure and functional roles of Epac2 (Rapgef4). Gene. 2016;575:577-83 pubmed publisher
    b>Epac (exchange protein activated by cyclic-AMP) 2 is a direct target of 3'-5'-cyclic adenosine monophosphate (cAMP) and is involved in cAMP-mediated signal transduction through activation of the Ras-like small GTPase Rap...
  36. Sun Q, Wang D, Ai G, Tian L, Zhao L, Chen R, et al. Epac1 is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation. Folia Histochem Cytobiol. 2018;56:21-26 pubmed publisher
    The exchange protein directly activated by cAMP (Epac1), a downstream target of the second messenger cAMP, modulates multiple biological effects of cAMP, alone or in cooperation with protein kinase A (PKC)...
  37. Ohba Y, Kurokawa K, Matsuda M. Mechanism of the spatio-temporal regulation of Ras and Rap1. EMBO J. 2003;22:859-69 pubmed
    ..Here, we explored the mechanism underlying this phenomenon. We originally noticed that in cells expressing Epac, a cAMP-dependent Rap1 GEF (guanine nucleotide exchange factor), cAMP activated Rap1 at the perinuclear region, as ..
  38. Bingham T, Fisher E, Parathath S, Reiss A, Chan E, Cronstein B. A2A adenosine receptor stimulation decreases foam cell formation by enhancing ABCA1-dependent cholesterol efflux. J Leukoc Biol. 2010;87:683-90 pubmed publisher
    ..5% to 17.5+2.5% [3H]-cholesterol efflux; P<0.0090 vs. control; n=3) but not in ABCA1 KD cells. Activation of Epac, a signaling molecule downstream of the A2AR, increased ABCA1 (23+5%; P<0.0007 vs...
  39. Bala V, Rajagopal S, Kumar D, Nalli A, Mahavadi S, Sanyal A, et al. Release of GLP-1 and PYY in response to the activation of G protein-coupled bile acid receptor TGR5 is mediated by Epac/PLC-ε pathway and modulated by endogenous H2S. Front Physiol. 2014;5:420 pubmed publisher
    ..8-pCPT-2'-O-Me-cAMP, a selective activator of Epac, stimulated PI hydrolysis, and GLP-1 and PYY release...
  40. Ou Z, Sun Y, Lin L, You N, Liu X, Li H, et al. Olig2-Targeted G-Protein-Coupled Receptor Gpr17 Regulates Oligodendrocyte Survival in Response to Lysolecithin-Induced Demyelination. J Neurosci. 2016;36:10560-10573 pubmed
    ..We showed that Gpr17 inhibition elevated Epac1 expression and promoted oligodendrocyte differentiation...
  41. Noda K, Zhang J, Fukuhara S, Kunimoto S, Yoshimura M, Mochizuki N. Vascular endothelial-cadherin stabilizes at cell-cell junctions by anchoring to circumferential actin bundles through alpha- and beta-catenins in cyclic AMP-Epac-Rap1 signal-activated endothelial cells. Mol Biol Cell. 2010;21:584-96 pubmed publisher
    ..Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin-dependent cell adhesion...
  42. Adderley S, Sridharan M, Bowles E, Stephenson A, Sprague R, Ellsworth M. Inhibition of ATP release from erythrocytes: a role for EPACs and PKC. Microcirculation. 2011;18:128-35 pubmed publisher
    ..ISO), was determined in the absence and presence of selective phosphodiesterase inhibitors and/or the EPAC activator, 8CPT2OMecAMP (8CPT)...
  43. Lezoualc h F, Fazal L, Laudette M, Conte C. Cyclic AMP Sensor EPAC Proteins and Their Role in Cardiovascular Function and Disease. Circ Res. 2016;118:881-97 pubmed publisher
    ..The 2 EPAC isoforms, EPAC1 and EPAC2, are guanine-nucleotide exchange factors for the Ras-like GTPases, Rap1 and Rap2, which they activate ..
  44. Kaur S, Kong C, Cannell M, Ward M. Depotentiation of intact rat cardiac muscle unmasks an Epac-dependent increase in myofilament Ca(2+) sensitivity. Clin Exp Pharmacol Physiol. 2016;43:88-94 pubmed publisher
    ..In the heart, investigation of exchange protein directly activated by cAMP (Epac) has yielded conflicting results...
  45. Tao X, Mei F, Agrawal A, Peters C, Ksiazek T, Cheng X, et al. Blocking of exchange proteins directly activated by cAMP leads to reduced replication of Middle East respiratory syndrome coronavirus. J Virol. 2014;88:3902-10 pubmed publisher
    ..study, we revealed a novel positive function of an exchange protein directly activated by cyclic AMP 1 (cAMP-1; Epac-1) on MERS-CoV replication...
  46. Branham M, Bustos M, De Blas G, Rehmann H, Zarelli V, Trevino C, et al. Epac activates the small G proteins Rap1 and Rab3A to achieve exocytosis. J Biol Chem. 2009;284:24825-39 pubmed publisher
    ..The relevant cAMP target is Epac, a guanine nucleotide exchange factor for the small GTPase Rap...
  47. Ramos C, Lin C, Liu X, Antonetti D. The EPAC-Rap1 pathway prevents and reverses cytokine-induced retinal vascular permeability. J Biol Chem. 2018;293:717-730 pubmed publisher
    ..The cAMP-dependent guanine nucleotide exchange factor (EPAC) exchange-protein directly activated by cAMP promotes exchange of GTP in the small GTPase Rap1...
  48. Matsuda M, Oh hashi K, Yokota I, Sawa T, Amaya F. Acquired Exchange Protein Directly Activated by Cyclic Adenosine Monophosphate Activity Induced by p38 Mitogen-activated Protein Kinase in Primary Afferent Neurons Contributes to Sustaining Postincisional Nociception. Anesthesiology. 2017;126:150-162 pubmed
    ..Expression of two isoforms of EPAC (EPAC1/EPAC2) in dorsal root ganglions from naive rats and those 14 days after the incision was detected by ..
  49. Tao Y, Li L, Jiang B, Feng Z, Yang L, Tang J, et al. Cannabinoid receptor-2 stimulation suppresses neuroinflammation by regulating microglial M1/M2 polarization through the cAMP/PKA pathway in an experimental GMH rat model. Brain Behav Immun. 2016;58:118-129 pubmed publisher
    ..effectors, phosphorylated cAMP-dependent protein kinase (p-PKA) and exchange protein activated by cyclic-AMP 1 (Epac1)...
  50. Domínguez Rodríguez A, Ruiz Hurtado G, Sabourin J, Gómez A, Alvarez J, Benitah J. Proarrhythmic effect of sustained EPAC activation on TRPC3/4 in rat ventricular cardiomyocytes. J Mol Cell Cardiol. 2015;87:74-8 pubmed publisher
    The Exchange Protein directly Activated by cAMP (EPAC) participates to the pathological signaling of cardiac hypertrophy and heart failure, in which the role of Ca(2+) entry through the Transient Receptor Potential Canonical (TRPC) ..
  51. Wiejak J, Dunlop J, Yarwood S. The role of c-Jun in controlling the EPAC1-dependent induction of the SOCS3 gene in HUVECs. FEBS Lett. 2014;588:1556-61 pubmed publisher
    The cyclic AMP sensor, EPAC1, activates AP1-mediated transcription in HUVECs...
  52. Dupuy A, L Hoste S, Cherfils J, Camonis J, Gaudriault G, de Gunzburg J. Novel Rap1 dominant-negative mutants interfere selectively with C3G and Epac. Oncogene. 2005;24:4509-20 pubmed
    ..In cellular models where Rap1 is activated via endogenous GEFs, the Rap1[S17A] mutant inhibits both the cAMP-Epac and EGF-C3G pathways, whereas Rap1[G15D] selectively interferes with the latter...
  53. Zhu Y, Mei F, Luo P, Cheng X. A cell-based, quantitative and isoform-specific assay for exchange proteins directly activated by cAMP. Sci Rep. 2017;7:6200 pubmed publisher
    Extensive functional studies of the exchange protein directly activated by cAMP (EPAC) family of signaling molecules have demonstrated that EPAC proteins play a fundamental role in several physiological and pathophysiological responses, ..
  54. Wilson L, Baillie G, Pritchard L, Umana B, Terrin A, Zaccolo M, et al. A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells. J Biol Chem. 2011;286:16285-96 pubmed publisher
    ..objective of this study was to determine how a specific PDE3 variant, namely PDE3B, interacts with and regulates EPAC1-based signaling in human arterial endothelial cells (HAECs)...
  55. Grandoch M, Bujok V, Fleckenstein D, Schmidt M, Fischer J, Weber A. Epac inhibits apoptosis of human leukocytes. J Leukoc Biol. 2009;86:847-9 pubmed publisher
    ..Thus far, most of the cAMP-dependent effects have been attributed to the activation of PKA. However, Epac proteins (direct cAMP targets and guanine nucleotide exchange factors for Ras-like GTPases) have been shown ..
  56. Gao M, Ma Y, Bast R, Li Y, Wan L, Liu Y, et al. Epac1 knockdown inhibits the proliferation of ovarian cancer cells by inactivating AKT/Cyclin D1/CDK4 pathway in vitro and in vivo. Med Oncol. 2016;33:73 pubmed publisher
    ..Epac proteins, including Epac1 and Epac2, are implicated in several diverse cellular responses, such as insulin secretion, exocytosis, cellular ..
  57. Chang C, Cheong M, Chang G, Tsai M, Chen H. Involvement of Epac1/Rap1/CaMKI/HDAC5 signaling cascade in the regulation of placental cell fusion. Mol Hum Reprod. 2013;19:745-55 pubmed publisher
    ..cAMP enhances GCM1 desumoylation through the Epac1/Rap1/CaMKI signaling cascade and CaMKI is known to down-regulate class IIa HDAC activity...
  58. Garay J, D Angelo J, Park Y, Summa C, Aiken M, Morales E, et al. Crosstalk between PKA and Epac regulates the phenotypic maturation and function of human dendritic cells. J Immunol. 2010;185:3227-38 pubmed publisher
    ..through protein kinase A (PKA), it is now clear that cAMP also activates exchange protein activated by cAMP (Epac), a second major cAMP effector...
  59. Son I, Selvaratnam R, Dubins D, Melacini G, Chalikian T. Ultrasonic and densimetric characterization of the association of cyclic AMP with the cAMP-binding domain of the exchange protein EPAC1. J Phys Chem B. 2013;117:10779-84 pubmed publisher
    ..techniques to characterize the volumetric properties of the association of the cAMP-binding domain (CBD) of EPAC1 with cAMP at 25 °C in a pH 7.6 buffer...
  60. Umapathy N, Zemskov E, Gonzales J, Gorshkov B, Sridhar S, Chakraborty T, et al. Extracellular beta-nicotinamide adenine dinucleotide (beta-NAD) promotes the endothelial cell barrier integrity via PKA- and EPAC1/Rac1-dependent actin cytoskeleton rearrangement. J Cell Physiol. 2010;223:215-23 pubmed publisher
    ..Our studies also show the involvement of cAMP-dependent protein kinase A and EPAC1 pathways as well as small GTPase Rac1 in beta-NAD-induced EC barrier enhancement...
  61. Miklos W, Heffeter P, Pirker C, Hager S, Kowol C, Van Schoonhoven S, et al. Loss of phosphodiesterase 4D mediates acquired triapine resistance via Epac-Rap1-Integrin signaling. Oncotarget. 2016;7:84556-84574 pubmed publisher
    ..the protein kinase A (PKA)-cAMP response element-binding protein (Creb) and the exchange protein activated by cAMP (Epac)-Ras-related protein 1 (Rap1) signaling axes, was observed in SW480/tria cells...
  62. Yoshie M, Kaneyama K, Kusama K, Higuma C, Nishi H, Isaka K, et al. Possible role of the exchange protein directly activated by cyclic AMP (Epac) in the cyclic AMP-dependent functional differentiation and syncytialization of human placental BeWo cells. Hum Reprod. 2010;25:2229-38 pubmed publisher
    ..b>Epac1 and Epac2 were localized in human placental tissue (n = 9) by immunohistochemistry...
  63. Sheikh I, Koley H, Chakrabarti M, Hoque K. The Epac1 signaling pathway regulates Cl- secretion via modulation of apical KCNN4c channels in diarrhea. J Biol Chem. 2013;288:20404-15 pubmed publisher
    ..However, its role in diarrhea and regulation by Epac1 is unknown...
  64. Enserink J, Price L, Methi T, Mahic M, Sonnenberg A, Bos J, et al. The cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through the alpha3beta1 integrin but not the alpha6beta4 integrin. J Biol Chem. 2004;279:44889-96 pubmed
    ..adhesion and spreading on laminin-5, a process that is independent of protein kinase A but rather dependent on Epac1, a cAMP-dependent exchange factor for Rap...
  65. Huang S, Wettlaufer S, Chung J, Peters Golden M. Prostaglandin E2 inhibits specific lung fibroblast functions via selective actions of PKA and Epac-1. Am J Respir Cell Mol Biol. 2008;39:482-9 pubmed publisher
    ..to investigate the roles of the cAMP effectors protein kinase A (PKA) and exchange protein activated by cAMP-1 (Epac-1) in modulating these two functions in primary human fetal lung IMR-90 fibroblasts...
  66. DiPilato L, Cheng X, Zhang J. Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments. Proc Natl Acad Sci U S A. 2004;101:16513-8 pubmed
    ..fluorescent indicators that report intracellular cAMP dynamics and Epac activation by sandwiching the full-length Epac1 between cyan and yellow mutants of GFP...
  67. Sun W, Jiao W, Huang Y, Li R, Zhang Z, Wang J, et al. Exchange proteins directly activated by cAMP induce the proliferation of rat anterior pituitary GH3 cells via the activation of extracellular signal-regulated kinase. Biochem Biophys Res Commun. 2017;485:355-359 pubmed publisher
    ..the proliferation of GH3 cells and the phosphorylation of ERK1/2, and these effects were inhibited by PKA or Epac inhibitors...
  68. van Hooren K, van Agtmaal E, Fernandez Borja M, van Mourik J, Voorberg J, Bierings R. The Epac-Rap1 signaling pathway controls cAMP-mediated exocytosis of Weibel-Palade bodies in endothelial cells. J Biol Chem. 2012;287:24713-20 pubmed publisher
    ..cAMP-mediated signaling pathway in the regulation of WPB exocytosis, namely the guanine nucleotide exchange factor Epac1 and its substrate, the small GTPase Rap1...
  69. Lai T, Lin S, Lee H, Fan J, Hsu Y, Wang H, et al. HIF-1? binding to the Epac1 promoter recruits hematopoietic stem cells to the ischemic brain following stroke. J Mol Cell Biol. 2012;4:184-7 pubmed publisher
  70. Clemente M, Alvarez S, Serramía M, Martínez Bonet M, Muñoz Fernández M. Prostaglandin E2 reduces the release and infectivity of new cell-free virions and cell-to-cell HIV-1 transfer. PLoS ONE. 2014;9:e85230 pubmed publisher
    ..PGE2 effects were mimicked by dbcAMP and by a specific Epac (exchange protein directly activated by cyclic AMP) agonist, 8-Cpt-cAMP...
  71. Banerjee U, Cheng X. Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics. Gene. 2015;570:157-67 pubmed publisher
    Mammalian exchange protein directly activated by cAMP isoform 1 (EPAC1), encoded by the RAPGEF3 gene, is one of the two-membered family of cAMP sensors that mediate the intracellular functions of cAMP by acting as guanine nucleotide ..
  72. Pannekoek W, van Dijk J, Chan O, Huveneers S, Linnemann J, Spanjaard E, et al. Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control. Cell Signal. 2011;23:2056-64 pubmed publisher
    b>Epac1 and its effector Rap1 are important mediators of cAMP induced tightening of endothelial junctions and consequential increased barrier function...
  73. Guibinga G, Murray F, Barron N, Pandori W, Hrustanovic G. Deficiency of the purine metabolic gene HPRT dysregulates microRNA-17 family cluster and guanine-based cellular functions: a role for EPAC in Lesch-Nyhan syndrome. Hum Mol Genet. 2013;22:4502-15 pubmed publisher
    ..Most notably, our data show that the expression of the exchange protein activated by cAMP (EPAC) is blunted in HPRT-deficient human neuron-like cell lines and fibroblast cells from LNS patients, and is altered ..
  74. Gu Y, Wang C, Li G, Huang L. EXPRESS: F-actin links Epac-PKC signaling to purinergic P2X3 receptors sensitization in dorsal root ganglia following inflammation. Mol Pain. 2016;12: pubmed publisher
    ..This increase promotes the activation of PKC to produce a much enhanced PGE2 effect on ATP currents and to elicit Epac-dependent flinch nocifensive behavioral responses in complete Freund’s adjuvant rats...