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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.
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.
Study identifies Epac2-Rap1 signaling as a novel feedback mechanism in the heart, which controls mitochondrial reactive oxygen species production.
rs17746510, one of the three single-nucleotide polymorphisms (SNPs) in RAPGEF4 associated with cognitive decline in Chinese Alzheimer's disease (AD) patients, was significantly correlated with apathy and mood disturbance
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]
Data show that Epac2 is activated by cAMP and changes its structure. It is involved in cAMP-mediated signal transduction through activation of the Ras-like small GTPase and is expressed mainly in brain, neuroendocrine and endocrine tissues. [review]
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.
CALR regulated by EPAC2 in endometrial glandular epithelial cells is critical for the expression of LIF and PTGS2-mediated production of PGE2 through cAMP signaling.
Follow-up replication analyses in up to an additional 21,345 participants identified three new fasting plasma glucose loci reaching genome-wide significance in or near PDK1-RAPGEF4, KANK1, and IGF1R.
EPAC1 and EPAC2 are critical signaling intermediates in osteoclast differentiation that permit RANKL-stimulated NFkB nuclear translocation and actin rearrangements
data show the expression of EPAC is blunted in HPRT-deficient neuron-like cell lines and fibroblast cells from Lesch-Nyhan syndrome (LNS) patients; propose that the alterations in EPAC/RAP1 signaling and cell migration in HPRT deficiency are crucial for neuro-developmental events that may contribute to neurological dysfunctions in LNS
EPAC2-mediated CRT expression is essential for the functional and morphological differentiation of endometrial stromal cells into decidual cells
Cigarette smoke extract decreased Epac1 expression, but did not affect Epac2 and PKA expression.
Mechanism of intracellular cAMP sensor Epac2 activation: cAMP-induced conformational changes identified by amide hydrogen/deuterium exchange mass spectrometry
An important time-limited role is identified for hippocampal Epac2 signaling in cognition, opening new avenues to investigate the molecular mechanisms underlying memory retrieval.
Epac2 & Epac1 signaling pathways may be associated with cAMP-mediated functional differentiation and syncytialization of trophoblasts. Expression of Epac2 & Epac 1 in placenta at different stages was investigated.
Studies demonstrate the occurrence of the EPAC2 splicing variant EPAC2B in adrenocortical cancer cells and reveal the involvement of EPAC2B in cAMP-induced effects on cytoskeleton integrity and cell migration.
Mutations in the hinge of Epac can uncouple cAMP binding from its exchange activity.
variants were present in five families, where they segregate with the autistic phenotype.
a novel protein-binding partner for EPAC1 and EPAC2, light chain 2 of MAP1A (microtubule-associated protein 1A)
Deletion of exchange proteins directly activated by cAMP (Epac) causes defects in hippocampal signaling in female mice
Epac2(-/-) mice exhibited a wide range of mood disorders, including anxiety and depression with learning and memory deficits in contextual and cued fear-conditioning tests without affecting Epac1 expression or PKA activity.
PACAP could trigger astrocytic differentiation of neural stem cells via Epac2 activation.
Epac2, but not Epac1 has a role in decreasing severity of ischemic retinopathy after retinal ischemia/reperfusion injury
cAMP-GEF II plays a key role in hippocampal functions including behavioral flexibility.
data suggest that cAMP elevation uses an Epac2-dependent pathway to promote transmitter release, and that Epac2 is required to maintain the readily releasable pool at Mossy Fiber synapses in the hippocampus.
Epac1 primarily is capable of inhibiting remodeling processes, whereas Epac2 primarily increases inflammatory processes in vivo
Data suggest that sulfonylureas stabilize Epac2A in its open, active state and provide insight for the development of drugs that target Epac2A.
data show the expression EPAC is altered in the cortex, striatum and midbrain of HPRT knockout mouse; propose that the alterations in EPAC/RAP1 signaling and cell migration in HPRT deficiency are crucial for neuro-developmental events that may contribute to neurological dysfunctions in Lesch-Nyhan syndrome
DNA methylation of alternative promoters directs tissue specific expression of Epac2 isoforms.
Epac2 localization is dynamically controlled by cAMP as well as by Ca(2+)-mediated activation of Ras.
EPAC2A is required for potentiating the early dynamic increase in islet calcium levels after glucose stimulation, which is reflected in potentiated first-phase insulin secretion.
there is a gut-heart GLP-1R-dependent and ANP-dependent axis that regulates blood pressure and involves Epac2
beta1-induced adrenergic-dependent arrhythmias are less inducible in Epac2-knockout versus wild-type mice.
This study demonistrated that exhibited specific impairments in social and communication behavior displayed specific alterations in cortical columnar organization in the somatosensory cortex.
analysis of autoinhibition and activation of the exchange protein directly activated by cyclic AMP (EPAC) and EPAC2
Phospholipase c-epsilon is a determinant of mouse islet insulin secretion that is under the control of Epac2.
Phospholipase C-eta was found to be expressed in mouse beta-cells, and knockout of that gene disrupts the action of exendin-4 to facilitate calcium-induced calcium release in the beta-cells of these mice.
Piccolo serves as a Ca(2+) sensor in exocytosis in pancreatic beta-cells and the formation of a cAMP-GEFII.Rim2.Piccolo complex is important in cAMP-induced insulin secretion
Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA- independent exocytosis through interaction with RIMS2 (By similarity).
Rap guanine nucleotide exchange factor (GEF) 4
, rap guanine nucleotide exchange factor 4
, rap guanine nucleotide exchange factor 4-like
, EPAC 2
, RAP guanine-nucleotide-exchange factor (GEF) 4
, cAMP-regulated guanine nucleotide exchange factor II
, exchange factor directly activated by cAMP 2
, exchange protein directly activated by cAMP 2
, putative protein product of Nbla00496
, cAMP-dependent Rap1 guanine-nucleotide exchange factor
, cAMP-regulated guanine nucleotide exchange factor IIB
, epac 2