Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics (Q28608179)

Structure-guided design of selective Epac1 and Epac2 agonists

Europe PubMed Central

title

Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics (English)

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part of the series

Gene Wiki Review Series

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Xiaodong Cheng

2

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author name string

Upasana Banerjee

series ordinal

1

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language of work or name

English

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publication date

10 October 2015

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published in

Gene

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volume

570

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page(s)

157-67

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issue

2

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cites work

1 reference

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Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions

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Structural Analyses of a Constitutively Active Mutant of Exchange Protein Directly Activated by cAMP

17 March 2017

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GRK2: multiple roles beyond G protein-coupled receptor desensitization

17 March 2017

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A fluorescence-based high-throughput assay for the discovery of exchange protein directly activated by cyclic AMP (EPAC) antagonists

17 March 2017

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A phosphodiesterase 3B-based signaling complex integrates exchange protein activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human arterial endothelial cells

17 March 2017

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Radixin assembles cAMP effectors Epac and PKA into a functional cAMP compartment: role in cAMP-dependent cell proliferation

17 March 2017

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Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B

17 March 2017

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Renal expression of exchange protein directly activated by cAMP (Epac) 1 and 2

17 March 2017

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Epac mediates beta-adrenergic receptor-induced cardiomyocyte hypertrophy

17 March 2017

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Numerous distinct PKA-, or EPAC-based, signalling complexes allow selective phosphodiesterase 3 and phosphodiesterase 4 coordination of cell adhesion

17 March 2017

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Cell physiology of cAMP sensor Epac

17 March 2017

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Rap1-mediated activation of extracellular signal-regulated kinases by cyclic AMP is dependent on the mode of Rap1 activation

17 March 2017

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The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways.

17 March 2017

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Exchange protein directly activated by cAMP (EPAC) interacts with the light chain (LC) 2 of MAP1A

17 March 2017

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Structural basis for modulation and agonist specificity of HCN pacemaker channels

17 March 2017

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Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs

17 March 2017

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A family of cAMP-binding proteins that directly activate Rap1

17 March 2017

1 reference

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Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP

17 March 2017

1 reference

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The structural basis of the activation of Ras by Sos

17 March 2017

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Proteins regulating Ras and its relatives

17 March 2017

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Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domains

17 March 2017

1 reference

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Biochemical and pharmacological characterizations of ESI-09 based EPAC inhibitors: defining the ESI-09 "therapeutic window".

17 March 2017

1 reference

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Pharmacological inhibition and genetic knockdown of exchange protein directly activated by cAMP 1 reduce pancreatic cancer metastasis in vivo

29 September 2017

1 reference

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Exchange protein directly activated by cAMP modulates regulatory T-cell-mediated immunosuppression

29 September 2017

1 reference

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Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Epac1 increases migration of endothelial cells and melanoma cells via FGF2-mediated paracrine signaling

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Epac proteins: specific ligands and role in cardiac remodelling.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Blocking of exchange proteins directly activated by cAMP leads to reduced replication of Middle East respiratory syndrome coronavirus

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways

29 September 2017

1 reference

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Recent advances in the discovery of small molecules targeting exchange proteins directly activated by cAMP (EPAC).

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Cyclic AMP sensor EPAC proteins and energy homeostasis

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Balancing GRK2 and EPAC1 levels prevents and relieves chronic pain.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

A role for Piezo2 in EPAC1-dependent mechanical allodynia.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Efficient Synthesis of ESI-09, A Novel Non-cyclic Nucleotide EPAC Antagonist

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Epac2 mediates cardiac β1-adrenergic-dependent sarcoplasmic reticulum Ca2+ leak and arrhythmia.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Identification and characterization of small molecules as potent and specific EPAC2 antagonists

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP isoform 1

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Identification of a tetrahydroquinoline analog as a pharmacological inhibitor of the cAMP-binding protein Epac

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Isoform-specific antagonists of exchange proteins directly activated by cAMP

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

A novel EPAC-specific inhibitor suppresses pancreatic cancer cell migration and invasion

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Creating order from chaos: cellular regulation by kinase anchoring

29 September 2017

1 reference

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Transient decrease in nociceptor GRK2 expression produces long-term enhancement in inflammatory pain

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

5-Cyano-6-oxo-1,6-dihydro-pyrimidines as potent antagonists targeting exchange proteins directly activated by cAMP.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

cAMP regulates DEP domain-mediated binding of the guanine nucleotide exchange factor Epac1 to phosphatidic acid at the plasma membrane

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

The projection analysis of NMR chemical shifts reveals extended EPAC autoinhibition determinants.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Upregulation of mTORC2 activation by the selective agonist of EPAC, 8-CPT-2Me-cAMP, in prostate cancer cells: assembly of a multiprotein signaling complex

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

The myriad roles of cyclic AMP in microbial pathogens: from signal to sword

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Role of dynamics in the autoinhibition and activation of the exchange protein directly activated by cyclic AMP (EPAC)

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Epac1-mediated, high glucose-induced renal proximal tubular cells hypertrophy via the Akt/p21 pathway

29 September 2017

1 reference

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Regulating Rap small G-proteins in time and space

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

The nucleoporin RanBP2 tethers the cAMP effector Epac1 and inhibits its catalytic activity

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Epac1 promotes melanoma metastasis via modification of heparan sulfate.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Mechanism of intracellular cAMP sensor Epac2 activation: cAMP-induced conformational changes identified by amide hydrogen/deuterium exchange mass spectrometry (DXMS).

29 September 2017

1 reference

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Mapping allostery through the covariance analysis of NMR chemical shifts

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

AKAP9 regulation of microtubule dynamics promotes Epac1-induced endothelial barrier properties

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Low nociceptor GRK2 prolongs prostaglandin E2 hyperalgesia via biased cAMP signaling to Epac/Rap1, protein kinase Cepsilon, and MEK/ERK.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Spatial regulation of cyclic AMP-Epac1 signaling in cell adhesion by ERM proteins

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Exchange protein directly activated by cyclic AMP increases melanoma cell migration by a Ca2+-dependent mechanism

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

The interaction of Epac1 and Ran promotes Rap1 activation at the nuclear envelope

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Mechanism of Epac activation: structural and functional analyses of Epac2 hinge mutants with constitutive and reduced activities

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Direct spatial control of Epac1 by cyclic AMP.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

8-pCPT-2'-O-Me-cAMP-AM: an improved Epac-selective cAMP analogue.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

The cyclic AMP effector Epac integrates pro- and anti-fibrotic signals

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Role of Epac1, an exchange factor for Rap GTPases, in endothelial microtubule dynamics and barrier function

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Effects of prostaglandin E2 on the subcellular localization of Epac-1 and Rap1 proteins during Fcgamma-receptor-mediated phagocytosis in alveolar macrophages

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Epac-selective cAMP analogs: new tools with which to evaluate the signal transduction properties of cAMP-regulated guanine nucleotide exchange factors

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Interactome of transforming growth factor-beta type I receptor (TbetaRI): inhibition of TGFbeta signaling by Epac1.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Capturing cyclic nucleotides in action: snapshots from crystallographic studies

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Interplay between exchange protein directly activated by cAMP (Epac) and microtubule cytoskeleton

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC).

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Fluorescent indicators of cAMP and Epac activation reveal differential dynamics of cAMP signaling within discrete subcellular compartments

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that Epac and cAMP kinase act synergistically to promote PC-12 cell neurite extension

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Communication between the regulatory and the catalytic region of the cAMP-responsive guanine nucleotide exchange factor Epac

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Cell cycle-dependent subcellular localization of exchange factor directly activated by cAMP.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

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

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

The cAMP sensors, EPAC1 and EPAC2, display distinct subcellular distributions despite sharing a common nuclear pore localisation signal.

29 September 2017

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Cyclic AMP phosphodiesterase 4D (PDE4D) Tethers EPAC1 in a vascular endothelial cadherin (VE-Cad)-based signaling complex and controls cAMP-mediated vascular permeability

3 June 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Exchange protein directly activated by cAMP 1 promotes autophagy during cardiomyocyte hypertrophy.

3 June 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

HIF-1α binding to the Epac1 promoter recruits hematopoietic stem cells to the ischemic brain following stroke.

27 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Bacillus anthracis edema toxin suppresses human macrophage phagocytosis and cytoskeletal remodeling via the protein kinase A and exchange protein activated by cyclic AMP pathways

27 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

The cAMP/Epac1/Rap1 pathway in pancreatic carcinoma

27 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Cyclic nucleotide analogs as probes of signaling pathways.

27 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Structural dynamics in the activation of Epac.

27 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Understanding cAMP-dependent allostery by NMR spectroscopy: comparative analysis of the EPAC1 cAMP-binding domain in its apo and cAMP-bound states.

27 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

Epac mediates a cAMP-to-PKC signaling in inflammatory pain: an isolectin B4(+) neuron-specific mechanism.

27 November 2018

1 reference

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pmc&linkname=pmc_refs_pubmed&retmode=json&id=4556420

The (R)-enantiomer of CE3F4 is a preferential inhibitor of human exchange protein directly activated by cyclic AMP isoform 1 (Epac1)

27 November 2018

1 reference

12 December 2020

An adenosine 3',5'-monophosphate-dependant protein kinase from rabbit skeletal muscle

1 reference

12 December 2020

Formation of a cyclic adenine ribonucleotide by tissue particles

1 reference

12 December 2020

Both protein kinase A and exchange protein activated by cAMP coordinate adhesion of human vascular endothelial cells

1 reference

12 December 2020

Specific interactions between Epac1, β-arrestin2 and PDE4D5 regulate β-adrenergic receptor subtype differential effects on cardiac hypertrophic signaling

1 reference

12 December 2020

Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1

1 reference

12 December 2020

Entropy-driven cAMP-dependent Allosteric Control of Inhibitory Interactions in Exchange Proteins Directly Activated by cAMP

1 reference

12 December 2020

A critical role of the cAMP sensor Epac in switching protein kinase signalling in prostaglandin E2-induced potentiation of P2X3 receptor currents in inflamed rats

1 reference

12 December 2020