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

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)

    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
    Pages (from-to)989-996
    Number of pages8
    JournalCellular Signalling
    Volume27
    Issue number5
    DOIs
    Publication statusPublished - May 2015

    Keywords

    • Catalytic Domain
    • Cyclic AMP
    • Guanine Nucleotide Exchange Factors
    • HEK293 Cells
    • Humans
    • Models, Molecular
    • Nuclear Localization Signals
    • Nuclear Pore

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