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Epac: a new cAMP target and new avenues in cAMP research

Abstract

Five years ago, Epac — a guanine nucleotide exchange factor for the Ras-like small GTPases Rap1 and Rap2 — was found to be a new target of cyclic AMP, which opened up new avenues for cAMP research. Structural analysis of the cAMP-binding domains of Epac2 has identified a unifying mechanism for how cAMP activates proteins, and the design and synthesis of an Epac-specific cAMP analogue has paved the way for future discoveries.

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Figure 1: The domain structure of Epac1 and Epac2.
Figure 2: cAMP-binding pockets and Epac activation.
Figure 3: Epac-specific cAMP analogue.
Figure 4: Distinct regulation of Ras and Rap1 by cAMP.
Figure 5: Epacs, cell adhesion and insulin secretion.

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Acknowledgements

I would like to thank F. Zwartkruis and H. Rehmann for critically reading this manuscript. The work on Epac in our lab is supported by the Dutch Cancer Society, the Netherlands Organization for Scientific Research (Council for Earth and Life Sciences and Council for Chemical Sciences) and the Human Frontiers Science Program.

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Interpro

cyclic-nucleotide-binding domain

GEF

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Epacs

ERK

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Epac2

Raf1

Rap1

Rap2

Rap2B

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Bos, J. Epac: a new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 4, 733–738 (2003). https://doi.org/10.1038/nrm1197

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