Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown

Houslay, M. D. (2010) Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends in Biochemical Sciences, 35(2), pp. 91-100. (doi:10.1016/j.tibs.2009.09.007)

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Publisher's URL: http://dx.doi.org/10.1016/j.tibs.2009.09.007

Abstract

It is becoming increasingly apparent that spatial regulation of cell signalling processes is critical to normal cellular function. In this regard, cAMP signalling regulates many pivotal cellular processes and has provided the paradigm for signal compartmentalization. Recent advances show that isoforms of the cAMP-degrading phosphodiesterase-4 (PDE4) family are targeted to discrete signalling complexes. There they sculpt local cAMP gradients that can be detected by genetically encoded cAMP sensors, and gate the activation of spatially localized signalling through sequestered PKA and EPAC sub-populations. Genes for these important regulatory enzymes are linked to schizophrenia, stroke and asthma, thus indicating the therapeutic potential that selective inhibitors could have as anti-inflammatory, anti-depressant and cognitive enhancer agents

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Houslay, Professor Miles
Authors: Houslay, M. D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Trends in Biochemical Sciences
Publisher:Elsevier
ISSN:0968-0004
ISSN (Online):1362-4326
Published Online:26 October 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438301Phosphodiesterase-4 isoforms - intracellular targeting, regulation and potential therapeutic targetsMiles HouslayMedical Research Council (MRC)G0600765Institute of Neuroscience and Psychology
421571thera-cAMP: identification of therapeutic molecules to target compartmentalised cAMP signalling networks in human diseaseMiles HouslayEuropean Commission (EC)UNSPECIFIEDInstitute of Neuroscience and Psychology
432501Transatlantic networks of excellence in cardiovascular diseaseMiles HouslayFoundation Leducq (LEDUCQ-VIL)06 CVD 02Institute of Neuroscience and Psychology