Disease relevance of Rapgef3

• cAMP-binding protein Epac induces cardiomyocyte hypertrophy [1].
• Also, in a behavioral model, cAMP produced mechanical hyperalgesia (tenderness) through Epac, PLC/PLD, and PKCepsilon [2].

High impact information on Rapgef3

• Antibodies directed against either the cAMP-activated guanine-nucleotide exchange factor Epac I, the monomeric G protein Rap-1 or the kinase Raf-B, curtailed the stimulation of H,K-ATPase by calcitonin, whereas antibodies against the related monomeric G protein Ras or kinase Raf-1 had no effect [3].
• The role of Rap1 in ERK and Akt activity was further demonstrated by our observation that an active form of Epac, which activated Rap1 in the absence of cAMP, increased ERK and Akt phosphorylation [4].
• However, neither exchange protein activated by cAMP (Epac) inhibitor brefeldin A nor hyperpolarization and cyclic nucleotide-activated channel blocker 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride (ZD7288) affected forskolin response [5].
• Contribution of the adenylyl cyclase-dependent pathway to activation of the currents depended on Epac (exchange protein directly activated by cAMP), but not on protein kinase A. The activation of Ca2+ and Cl- channels is likely to play a key role in the mechanisms by which glucagon regulates hepatocyte metabolism and volume [6].
• Exposure to cAMP and beta-adrenergic stimulation recruits Ca(V)3 T-type channels in rat chromaffin cells through Epac cAMP-receptor proteins [7].

Biological context of Rapgef3

• Neither protein kinase A nor Epac (Exchange protein directly activated by cAMP), two known direct effectors of cAMP, mediated the cAMP-induced inhibition of ERK and Akt phosphorylation [4].
• H89, a PKA inhibitor, did not affect OPC3911-mediated inhibition of insulin-induced glucose uptake and lipogenesis, whereas 8-pCPT-2'-O-Me-cAMP, an Epac agonist which mediates PKA independent cAMP signaling events, mimicked all the effects of OPC3911 [8].
• These results indicated that amylase release by beta-adrenergic stimulation is mediated through both the cAMP/PKA and cAMP/Epac signal pathways [9].
• Blockade of either calcineurin or Rac activity blunts the hypertrophic response elicited by Epac indicating these signaling molecules coordinately regulate cardiac gene expression and cellular growth [1].

Anatomical context of Rapgef3

• Enhanced functional gap junction neoformation by protein kinase A-dependent and Epac-dependent signals downstream of cAMP in cardiac myocytes [10].
• Here we demonstrated that the gating function of GJ is enhanced by the protein kinase A (PKA)-dependent signal, and that the accumulation of connexin43 (Cx43), the most abundant Cx in myocytes, is enhanced by an exchange protein directly activated by cAMP (Epac) (Rap1 activator)-dependent signal [10].
• Evidence for the involvement of cAMP-GEF (Epac) pathway in amylase release from the rat parotid gland [9].
• The Epac was localized in the intracellular and the plasma membrane fractions [9].
• Intracellular application of the selective Epac agonist 8-(4-chlorophenylthio)-2'-O-methyl-cAMP into presynaptic terminals potentiated EPSCs, suggesting that Epac is the main target of cAMP-induced synaptic potentiation [11].

Associations of Rapgef3 with chemical compounds

• In line with this, the selective Epac agonist 8CPT-2Me-cAMP nicely mimicked the action of pCPT-cAMP and isoprenaline, suggesting the existence of a dominant Epac-dependent recruitment of T-type channels in RCCs that may originate from the activation of beta-adrenoceptors [7].
• Our results suggest that ZG cells, in addition to PKA and Epac/Rap proteins, contain other as yet unidentified cAMP mediator(s) involved in regulating CaMK activity and aldosterone secretion [12].

Regulatory relationships of Rapgef3

• Coupling of neuronal 5-HT7 receptors to activation of extracellular-regulated kinase through a protein kinase A-independent pathway that can utilize Epac [13].

References