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prostacyclin regulates bone growth via the Epac/Rap1 pathway
cAMP binds Xepac protein enabling it to activate the Ca2+ pathway, which is necessary to start and maintain X. laevis vitellogenin uptake.
EPAC1 supports triple negative breast cancer-induced angiogenesis, tumor cell migration and invasiveness as well as pro-metastatic phenotypes in endothelial cells induced through the tumor secretome
Through isoform-specific gene knockdown, the authors found that EPAC2, but not EPAC1, plays a dominant role in controlling RSV replication and virus-induced host responses.
Epac1 can restore normal insulin signaling in the retinal vasculature through reductions in inflammatory cytokines
EPAC1inhibits AnxA2 surface translocation and plasminogen activation via PLCepsilon-PKC pathway.
Cyclic AMP (cAMP), a secondary messenger responsible for various physiological processes regulates cell metabolism by activating Protein kinase A (PKA) and by targeting exchange protein directly activated by cAMP (EPAC). EPAC is present in two isoforms EPAC1 and EPAC2, which exhibit different tissue distribution and is involved in GDP/GTP exchange along with activating Rap1- and Rap2-mediated signaling pathways.
These data reveal a MAPK pathway-independent switch in response to cAMP signaling during melanoma progression.Implications: The prosurvival mechanism involving the cAMP-EPAC-RAP1 signaling pathway suggest the potential for new targeted therapies in melanoma.
Authors show that blockade of cAMP signaling using MDL12330A led to an increase in PUMA transcript levels, but not p21 in melanoma cells. Results suggest that transcriptional repression is one of the functions of the cAMP-Epac signaling pathway.
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.
Data show that the Epac-Rap1 signaling axis is involved in triapine resistance.
This study indicates a novel role for Epac1 in PGE2-induced epithelial-to-mesenchymal transition and subsequent activation of beta-catenin
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.
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).
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
No significant association was observed between RAPGEF3 SNPs and the risk of Alzheimer's disease or neuropsychiatric inventory scores.
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]
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.
The contribution of EGFR, EPAC, and Ca(2+) in CDCA-induced activation of CFTR-dependent Cl(-) secretion.
Microtubule stabilization was further suggested by the finding that ascorbate increased the amount of Epac1 bound to alpha-tubulin.
during Epac1-induced activation of mTORC1 and mTORC2, Epac1 may have an additional function as a scaffold protein
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 deacetylates HMGB1 through increased IGFBP-3 and SIRT1 levels in the retinal vasculature.
Epac1 deficiency attenuates bFGF-induced VSMC migration, possibly via Akt/GSK3beta pathways.
the banding profile after Epac activation was altered by disruption of the cytoskeleton, suggesting that the orchestration of Epac-dependent PKC signaling is regulated in part by interactions with the cytoskeleton. The approach described here provides an effective means to characterize Epac-dependent PKC activity.
The activation of beta-adrenergic receptors in microglial cells triggers a cAMP-Epac-dependent and a cAMP-PKA-dependent cascade which affects phagocytosis via modulation of the swelling-activated Cl- current ICl,swell.
This study demonstrate that PKA signaling to Rap1b is a key signaling node for follicular thyroid carcinogenesis, while Epac1 activity is not required for tumor development.
the observed platelet phenotype is due to deficient Epac1 activity during megakaryopoiesis and thrombopoiesis, and that the defects in blood clotting for Epac1(-/-) is connected to secondary hemostasis.
Epac1 protects the retina against ischemia/reperfusion-induced neuronal and vascular damage
Mice with a genetic background of Tpo-Cre;Prkar1a(flox/flox);Epac1(-/-) are aggressive, and both the thyroid-specific knockout of Prkar1a and global knockout of Epac1 likely contribute to this aggressive behavior. This study supports the hypothesis that altered thyroid signaling and aggressive behavior are linked.
Deletion of exchange proteins directly activated by cAMP (Epac) causes defects in hippocampal signaling in female mice
The inactivation of EPAC1 affects the early stage of ebola virus entry.
Epac activation reduces inflammation and microvascular permeability in an acute lung injury model.
studies indicate that Epac1 plays important roles in promoting VSMC proliferation and phenotypic switch in response to vascular injury, therefore, representing a therapeutic target for vascular proliferative diseases.
These data indicate that Epac1 may be protective to the retina through inhibition of key inflammatory mediators.
Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts
In retinopathy, EPAC-1 expression is decreased in a microRNA-7-mediated manner, contributing to endothelial dysfunction.
Epac1 exerts a tonic inhibition of in vivo basal microvascular permeability
In behavioral tests, Epac1-/- mice exhibited similar phenotype to those of WT mice.
2-arachidonoylglycerol (2-AG) is an endogenous cannabinoid that depresses synaptic transmission through stimulation of CB1 receptors. Among the six isoforms of phospholipase C (PLC; PLCbeta, PLCgamma, PLCdelta, PLCepsilon, PLCzeta, PLCeta), only PLCbeta has been linked to 2-AG synthesis. Here we demonstrate that 8-CPT-2Me-cAMP, a selective agonist of the cAMP sensor protein Epac, enhances 2-AG-mediated synaptic depress...
Data suggest that Epac1 reduces formation of the NLRP3 inflammasome to reduce inflammatory responses in the retinal vasculature.
binds cAMP and activates the Ras superfamily guanine nucleotide binding protein (Rap1A)in a PKA-independent manner
Rap guanine nucleotide exchange factor (GEF) 3
, RAP guanine-nucleotide-exchange factor 3
, exchange protein directly activated by cAMP 1
, rap guanine nucleotide exchange factor 3
, Rap1 guanine-nucleotide exchange factor
, rap guanine nucleotide exchange factor 3-like
, EPAC 1
, Rap1 guanine-nucleotide-exchange factor directly activated by cAMP
, cAMP-regulated guanine nucleotide exchange factor I
, exchange factor directly activated by cAMP 1
, cAMP-regulated guanine nucleotide exchange factor I (cAMP-GEFI)
, epac 1