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 > School of Molecular Biosciences |
| 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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