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Molecular Basis of Protective Anti-Inflammatory Signalling by Cyclic AMP in the Vascular Endothelium

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Systems Biology for Signaling Networks

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Abstract

Prototypical second messenger cyclic AMP (cAMP) was originally thought to mediate its effects through activation of cAMP-dependent protein kinase (PKA). However, it is now clear that cells possess multiple alternative sensors of cAMP accumulation, of which the “exchange protein directly activated by cAMP” (Epac) proteins have been studied most intensively. This article will describe recent insights made into the molecular mechanisms by which Epac proteins mediate key protective effects of cAMP on two specific aspects of vascular endothelial cell function, namely barrier function and suppression of inflammatory signalling. It will also examine how integrative and unbiased global approaches are currently being deployed to answer several wider questions that have arisen from the identification of Epac as a trigger of gene transcription events and the E3 ubquitin ligase component “suppressor of cytokine signalling-3” (SOCS-3) as a key gene target regulated by this pathway.

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Authors and Affiliations

  1. Biochemistry and Cell Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland, UK

    Claire Rutherford & Timothy M. Palmer

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  1. Claire Rutherford
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  2. Timothy M. Palmer
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Correspondence to Timothy M. Palmer .

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  1. College of Natural Science, Dept. Biological Science, Department of Molecular Science and Tech, Suwon, 442-749, Korea, Republic of (South Korea)

    Sangdun Choi

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Rutherford, C., Palmer, T.M. (2010). Molecular Basis of Protective Anti-Inflammatory Signalling by Cyclic AMP in the Vascular Endothelium. In: Choi, S. (eds) Systems Biology for Signaling Networks. Systems Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5797-9_23

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