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

Euan Parnell, Brian O. Smith, Stephen J. Yarwood*

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)989-996
Number of pages8
JournalCellular Signalling
Volume27
Issue number5
DOIs
StatePublished - May 1 2015

Keywords

  • CAMP
  • EPAC
  • Nucleus
  • Targeting

ASJC Scopus subject areas

  • Cell Biology

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