The cAMP sensors, EPAC1 and EPAC2, display distinct subcellular distributions despite sharing a common nuclear pore localisation signal

Parnell, E., Smith, B. O. and Yarwood, S. J. (2015) The cAMP sensors, EPAC1 and EPAC2, display distinct subcellular distributions despite sharing a common nuclear pore localisation signal. Cellular Signalling, 27(5), pp. 989-996. (doi:10.1016/j.cellsig.2015.02.009) (PMID:25683912) (PMCID:PMC4372255)

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Abstract

We have identified a conserved nuclear pore localisation signal (NPLS; amino acids 764–838 of EPAC1) in the catalytic domains of the cAMP-sensors, EPAC1 and EPAC2A. Consequently, EPAC1 is mainly localised to the nuclear pore complex in HEK293T cells where it becomes activated following stimulation with cAMP. In contrast, structural models indicate that the cAMP-binding domain of EPAC2A (CNBD1) blocks access to the conserved NPLS in EPAC2A, reducing its ability to interact with nuclear binding sites. Consequently, a naturally occurring EPAC2 isoform, EPAC2B, which lacks CNBD1 is enriched in nuclear fractions, similar to EPAC1. Structural differences in EPAC isoforms may therefore determine their intracellular location and their response to elevations in intracellular cAMP.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Yarwood, Dr Stephen and Smith, Dr Brian and Parnell, Mr Euan
Authors: Parnell, E., Smith, B. O., and Yarwood, S. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Cellular Signalling
Publisher:Elsevier Inc.
ISSN:0898-6568
ISSN (Online):1873-3913
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Cellular Signalling 27(5):989-996
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
500151Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES
500152Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES