cAMP Activity Assay Kit 100 assays
- Known as:
- cAMP Activity Assay Kit 100 tests
- Catalog number:
- K371-100
- Product Quantity:
- 100 assays
- Category:
- Peptides
- Supplier:
- Biovis
- Gene target:
- cAMP Activity Assay Kit 100 assays
Related genes to: cAMP Activity Assay Kit 100 assays
- Gene:
- CAMP NIH gene
- Name:
- cathelicidin antimicrobial peptide
- Previous symbol:
- -
- Synonyms:
- CAP18, FALL39, FALL-39, LL37
- Chromosome:
- 3p21.31
- Locus Type:
- gene with protein product
- Date approved:
- 1996-12-12
- Date modifiied:
- 2016-10-05
- Gene:
- RAPGEF3 NIH gene
- Name:
- Rap guanine nucleotide exchange factor 3
- Previous symbol:
- -
- Synonyms:
- cAMP-GEFI, EPAC, bcm910
- Chromosome:
- 12q13.11
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-01
- Date modifiied:
- 2016-10-05
- Gene:
- RAPGEF4 NIH gene
- Name:
- Rap guanine nucleotide exchange factor 4
- Previous symbol:
- -
- Synonyms:
- cAMP-GEFII, CGEF2
- Chromosome:
- 2q31.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-01
- Date modifiied:
- 2016-10-05
Related products to: cAMP Activity Assay Kit 100 assays
Related articles to: cAMP Activity Assay Kit 100 assays
- Sulfonylureas (SUs) are a class of antidiabetic drugs widely used in the management of diabetes mellitus type 2. They promote insulin secretion by inhibiting the ATP-sensitive potassium channel in pancreatic β-cells. Recently, the exchange protein directly activated by cAMP (Epac) was identified as a new class of target proteins of SUs that might contribute to their antidiabetic effect, through the activation of the Ras-like guanosine triphosphatase Rap1, which has been controversially discussed. We used human embryonic kidney (HEK) 293 cells expressing genetic constructs of various Förster resonance energy transfer (FRET)-based biosensors containing different versions of Epac1 and Epac2 isoforms, alone or fused to different phosphodiesterases (PDEs), to monitor SU-induced conformational changes in Epac or direct PDE inhibition in real time. We show that SUs can both induce conformational changes in the Epac2 protein but not in Epac1, and directly inhibit the PDE3 and PDE4 families, thereby increasing cAMP levels in the direct vicinity of these PDEs. Furthermore, we demonstrate that the binding site of SUs in Epac2 is distinct from that of cAMP and is located between the amino acids E443 and E460. Using biochemical assays, we could also show that tolbutamide can inhibit PDE activity through an allosteric mechanism. Therefore, the cAMP-elevating capacity due to allosteric PDE inhibition in addition to direct Epac activation may contribute to the therapeutic effects of SU drugs. - Source: PubMed
Publication date: 2024/08/10
Berisha FilipBlankenberg StefanNikolaev Viacheslav O - The exchange protein directly activated by cAMP (EPAC) has been implicated in cardiac proarrhythmic signaling pathways including spontaneous diastolic Ca leak from sarcoplasmic reticulum and increased action potential duration (APD) in isolated ventricular cardiomyocytes. The action potential (AP) lengthening following acute EPAC activation is mainly due to a decrease of repolarizing steady-state K current (IK) but the mechanisms involved remain unknown. This study aimed to assess the role of EPAC1 and EPAC2 in the decrease of IK and to investigate the underlying signaling pathways. AP and K currents were recorded with the whole cell configuration of the patch-clamp technique in freshly isolated rat ventricular myocytes. EPAC1 and EPAC2 were pharmacologically activated with 8-(4-chlorophenylthio)-2'--methyl-cAMP acetoxymethyl ester (8-CPTAM, 10 µmol/L) and inhibited with R-Ce3F4 and ESI-05, respectively. Inhibition of EPAC1 and EPAC2 significantly decreased the effect of 8-CPTAM on APD and IK showing that both EPAC isoforms are involved in these effects. Unexpectedly, calmodulin-dependent protein kinase II (CaMKII) inhibition by AIP or KN-93, and Ca chelation by intracellular BAPTA, did not impact the response to 8-CPTAM. However, inhibition of PLC/PKC and nitric oxide synthase (NOS)/PKG pathways partially prevents the 8-CPTAM-dependent decrease of IK. Finally, the cumulative inhibition of PKC and PKG blocked the 8-CPTAM effect, suggesting that these two actors work along parallel pathways to regulate IK upon EPAC activation. On the basis of such findings, we propose that EPAC1 and EPAC2 are involved in APD lengthening by inhibiting a K current via both PLC/PKC and NOS/PKG pathways. This may have pathological implications since EPAC is upregulated in diseases such as cardiac hypertrophy. Exchange protein directly activated by cAMP (EPAC) proteins modulate ventricular electrophysiology at the cellular level. Both EPAC1 and EPAC2 isoforms participate in this effect. Mechanistically, PLC/PKC and nitric oxide synthase (NO)/PKG pathways are involved in regulating K repolarizing current whereas the well-known downstream effector of EPAC, calmodulin-dependent protein kinase II (CaMKII), does not participate. This may have pathological implications since EPAC is upregulated in diseases such as cardiac hypertrophy. Thus, EPAC inhibition may be a new approach to prevent arrhythmias under pathological conditions. - Source: PubMed
Publication date: 2024/07/10
Boileve ArthurRomito OlivierHof ThomasLevallois AuréliaBrard Laurad'Hers SarahFouchet AlexandreSimard ChristopheGuinamard RomainBrette FabienSallé Laurent - Exchange proteins directly activated by cAMP (EPAC) belong to a family of RAP guanine nucleotide exchange factors (RAPGEF). EPAC1/2 (RAPGEF3/4) activates RAP1 and the alternative cAMP signaling pathway. We previously showed that the differential growth response of primary and metastatic melanoma cells to cAMP is mediated by EPAC. However, the mechanisms responsible for this differential response to EPAC signaling are not understood. In this study, we show that pharmacologic inhibition or siRNA-mediated knockdown of EPAC selectively inhibits the growth and survival of primary melanoma cells by downregulation of cell-cycle proteins and inhibiting the cell-cycle progression independent of ERK1/2 phosphorylation. EPAC inhibition results in upregulation of AKT phosphorylation but a downregulation of mTORC1 activity and its downstream effectors. We also show that EPAC regulates both glycolysis and oxidative phosphorylation, and production of mitochondrial reactive oxygen species, preferentially in primary melanoma cells. Employing a series of genetically matched primary and lymph node metastatic (LNM) melanoma cells, and distant organ metastatic melanoma cells, we show that the LNM and metastatic melanoma cells become progressively less responsive and refractory to EPAC inhibition suggesting loss of dependency on EPAC signaling correlates with melanoma progression. Analysis of The Cancer Genome Atlas dataset showed that lower RAPGEF3, RAPGEF4 mRNA expression in primary tumor is a predictor of better disease-free survival of patients diagnosed with primary melanoma suggesting that EPAC signaling facilitates tumor progression and EPAC is a useful prognostic marker. These data highlight EPAC signaling as a potential target for prevention of melanoma progression. - Source: PubMed
Krishnan AishwaryaBhasker Aishwarya ISingh Mithalesh KRodriguez Carlos IPérez Edgardo CastroAltameemi SarahLares MarcosKhan HamidullahNdiaye MaryAhmad NihalSchieke Stefan MSetaluri Vijayasaradhi - Exchange proteins directly activated by cAMP (EPAC1 and EPAC2) are one of the several families of cellular effectors of the prototypical second messenger cAMP. To understand the origin and molecular evolution of EPAC proteins, we performed a comprehensive phylogenetic analysis of EPAC1 and EPAC2. Our study demonstrates that unlike its cousin PKA, EPAC proteins are only present in multicellular Metazoa. Within the EPAC family, EPAC1 is only associated with chordates, while EPAC2 spans the entire animal kingdom. Despite a much more contemporary origin, EPAC1 proteins show much more sequence diversity among species, suggesting that EPAC1 has undergone more selection and evolved faster than EPAC2. Phylogenetic analyses of the individual cAMP binding domain (CBD) and guanine nucleotide exchange (GEF) domain of EPACs, two most conserved regions between the two isoforms, further reveal that EPAC1 and EPAC2 are closely clustered together within both the larger cyclic nucleotide receptor and RAPGEF families. These results support the notion that EPAC1 and EPAC2 share a common ancestor resulting from a fusion between the CBD of PKA and the GEF from RAPGEF1. On the other hand, the two terminal extremities and the RAS-association (RA) domains show the most sequence diversity between the two isoforms. Sequence diversities within these regions contribute significantly to the isoform-specific functions of EPACs. Importantly, unique isoform-specific sequence motifs within the RA domain have been identified. - Source: PubMed
Publication date: 2021/10/14
Ni ZhuofuCheng Xiaodong - It has been shown that the antidiabetic drug metformin protects hepatocytes against toxicity by various stressors. Chronic or excessive consumption of diclofenac (DF) - a pain-relieving drug, leads to drug-induced liver injury via a mechanism involving mitochondrial damage and ultimately apoptotic death of hepatocytes. However, whether metformin protects against DF-induced toxicity is unknown. Recently, it was also shown that cAMP elevation is protective against DF-induced apoptotic death in hepatocytes, a protective effect primarily involving the downstream cAMP effector EPAC and preservation of mitochondrial function. This study therefore aimed at investigating whether metformin protects against DF-induced toxicity via cAMP-EPACs. - Source: PubMed
Publication date: 2021/08/28
Mora Fabio Alejandro AguilarMusheshe NshungeArroyave Ospina Johanna CGeng YanaSoto Juan MRodrigo José AAlieva TatianaBuist-Homan ManonLezoualc'h FrankCheng XiaodongSchmidt MartinaMoshage Han