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Epac: effectors and biological functions

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Abstract

Epac1 (also known as cAMP-GEF-I) and Epac2 (also known as cAMP-GEF-II) are cyclic AMP-activated guanine nucleotide exchange factors for Ras-like GTPases. Since their discovery about 10 years ago, it is now accepted that Epac proteins are novel cAMP sensors that regulate several pivotal cellular processes, including calcium handling, cell proliferation, cell survival, cell differentiation, cell polarization, cell–cell adhesion events, gene transcription, secretion, ion transport, and neuronal signaling. Recent studies even indicated that Epac proteins might play a role in the regulation of inflammation and the development of cardiac hypertrophy. Meanwhile, a plethora of diverse effectors of Epac proteins have been assigned, such as Ras and Rho GTPases, phospholiase C-ɛ, phospholipase D, mitogen-activated protein kinases, protein kinase B/Akt, ion channels, secretory-granule associated proteins and regulators of the actin-microtubule network, the latter probably involved in the spatiotemporal dynamics of Epac-related signaling. This review highlights multi-faceted effectors and diverse biological functions driven by Epac proteins that might explain certain controversial signaling properties of cAMP.

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Acknowledgement

Within the last 10 years, our knowledge about the impact of Epac-driven signaling routes has increased remarkably, and novel Epac-related signaling properties are published every week. Unfortunately, as for space limitations, we were not able to include all recent work on Epac. We thank Dr. Oude Weernink for critical reading of the manuscript. Sara S. Roscioni is recipient of an Ubbo Emmius Fellowship from the School of Behavioral and Cognitive Neurosciences (BCN), University of Groningen, and Martina Schmidt is a Rosalind Franklin Fellow at the University of Groningen.

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  1. Department of Molecular Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands

    Sara S. Roscioni, Carolina R. S. Elzinga & Martina Schmidt

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  1. Sara S. Roscioni
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  2. Carolina R. S. Elzinga
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  3. Martina Schmidt
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Correspondence to Martina Schmidt.

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Roscioni, S.S., Elzinga, C.R.S. & Schmidt, M. Epac: effectors and biological functions. Naunyn-Schmied Arch Pharmacol 377, 345–357 (2008). https://doi.org/10.1007/s00210-007-0246-7

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