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Rapgef3  -  Rap guanine nucleotide exchange factor...

Mus musculus

Synonyms: 2310016P22Rik, 9330170P05Rik, EPAC 1, Epac, Epac1, ...
 
 
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Disease relevance of Rapgef3

  • Here, we describe an optical technique to simultaneously image cAMP and Ca(2+) concentration gradients in MIN6 mouse insulinoma cells using Epac1-camps, a Förster (or fluorescence) resonance energy transfer (FRET)-based cAMP biosensor, and Fura-2, a fluorescent indicator of Ca(2+) [1].
 

High impact information on Rapgef3

  • Incubation of macrophages with forskolin also increased Epac1 and Rap1.GTP [2].
  • We conclude that forskolin mediates cellular proliferation via cAMP-dependent activation of both PKA and Epac [2].
  • Here, we used confocal microscopy, fluorescence resonance energy transfer, and insulin-secreting MIN6 cells expressing Epac1-camps, a biosynthetic unimolecular cAMP indicator, to better understand the role of intracellular Ca2+ in cAMP production [3].
  • By contrast, activation of PKA, but not Epac-1, suppressed AM production of leukotriene B(4) and TNF-alpha, whereas stimulation of either PKA or Epac-1 inhibited AM bactericidal activity and H(2)O(2) production [4].
  • Exchange protein directly activated by cyclic AMP 2 (Epac2, or cAMP-binding guanine nucleotide exchange factor-2) was found to be expressed in gut and pancreatic proglucagon-producing cell lines, whereas the Epac-pathway-specific cAMP analog, 8-pMeOPT-2'O-Me-cAMP, effectively stimulated ERK1/2 phosphorylation as well as proglucagon mRNA expression [5].
 

Biological context of Rapgef3

  • Role of the exchange protein directly activated by cyclic adenosine 5'-monophosphate (Epac) pathway in regulating proglucagon gene expression in intestinal endocrine L cells [5].
  • cAMP cascade (PKA, Epac, adenylyl cyclase, Gi, and phosphodiesterases) regulates myelin phagocytosis mediated by complement receptor-3 and scavenger receptor-AI/II in microglia and macrophages [6].
  • Mutational analysis suggests a model for cAMP-induced Epac activation with rigid body movement of the regulatory region, the features of which are universally conserved in cAMP-regulated proteins [7].
  • Epac proteins (exchange proteins directly activated by cAMP) are guanine-nucleotide-exchange factors (GEFs) for the small GTP-binding proteins Rap1 and Rap2 that are directly regulated by the second messenger cyclic AMP and function in the control of diverse cellular processes, including cell adhesion and insulin secretion [7].
 

Anatomical context of Rapgef3

  • CAMP activates Rap1 in differentiating mouse male germ cells: a new signaling pathway mediated by the cAMP-activated exchange factor Epac [8]?
 

Associations of Rapgef3 with chemical compounds

  • Two principal effector proteins for cAMP are protein kinase A (PKA) and cAMP-responsive guanine nucleotide exchange factor (Epac), a Rap GDP exchange factor [9].
 

Other interactions of Rapgef3

  • This was further demonstrated by the facts that the stimulatory effect of VIP on luciferase activity could be reversed by the PKA inhibitors H-89 and KT5720 and was mimicked by cyclic AMP analogues selective for PKA, but not by those selective for Epac [10].
  • In contrast, the Epac-specific cAMP analog 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8CPT-2Me-cAMP) activates Rap1 in the BV2 cells, but does not induce PKA activation, as judged by CREB phosphorylation [9].
 

Analytical, diagnostic and therapeutic context of Rapgef3

References

  1. Simultaneous optical measurements of cytosolic Ca2+ and cAMP in single cells. Harbeck, M.C., Chepurny, O., Nikolaev, V.O., Lohse, M.J., Holz, G.G., Roe, M.W. Sci. STKE (2006) [Pubmed]
  2. Coordinate regulation of forskolin-induced cellular proliferation in macrophages by protein kinase A/cAMP-response element-binding protein (CREB) and Epac1-Rap1 signaling: effects of silencing CREB gene expression on Akt activation. Misra, U.K., Pizzo, S.V. J. Biol. Chem. (2005) [Pubmed]
  3. Interplay of Ca2+ and cAMP signaling in the insulin-secreting MIN6 beta-cell line. Landa, L.R., Harbeck, M., Kaihara, K., Chepurny, O., Kitiphongspattana, K., Graf, O., Nikolaev, V.O., Lohse, M.J., Holz, G.G., Roe, M.W. J. Biol. Chem. (2005) [Pubmed]
  4. Cutting edge: macrophage inhibition by cyclic AMP (cAMP): differential roles of protein kinase A and exchange protein directly activated by cAMP-1. Aronoff, D.M., Canetti, C., Serezani, C.H., Luo, M., Peters-Golden, M. J. Immunol. (2005) [Pubmed]
  5. Role of the exchange protein directly activated by cyclic adenosine 5'-monophosphate (Epac) pathway in regulating proglucagon gene expression in intestinal endocrine L cells. Lotfi, S., Li, Z., Sun, J., Zuo, Y., Lam, P.P., Kang, Y., Rahimi, M., Islam, D., Wang, P., Gaisano, H.Y., Jin, T. Endocrinology (2006) [Pubmed]
  6. cAMP cascade (PKA, Epac, adenylyl cyclase, Gi, and phosphodiesterases) regulates myelin phagocytosis mediated by complement receptor-3 and scavenger receptor-AI/II in microglia and macrophages. Makranz, C., Cohen, G., Reichert, F., Kodama, T., Rotshenker, S. Glia (2006) [Pubmed]
  7. Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state. Rehmann, H., Das, J., Knipscheer, P., Wittinghofer, A., Bos, J.L. Nature (2006) [Pubmed]
  8. CAMP activates Rap1 in differentiating mouse male germ cells: a new signaling pathway mediated by the cAMP-activated exchange factor Epac? Berruti, G. Cell. Mol. Biol. (Noisy-le-grand) (2003) [Pubmed]
  9. Epac1-mediated Rap1 activation is not required for the production of nitric oxide in BV2, murine microglial cells. Moon, E.Y., Oh, S.Y., Han, G.H., Lee, C.S., Park, S.K. J. Neurosci. Res. (2005) [Pubmed]
  10. Increased expression of interleukin-6 by vasoactive intestinal peptide is associated with regulation of CREB, AP-1 and C/EBP, but not NF-kappaB, in mouse calvarial osteoblasts. Persson, E., Voznesensky, O.S., Huang, Y.F., Lerner, U.H. Bone (2005) [Pubmed]
 
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