The interaction of Epac1 and ran promotes Rap1 activation at the nuclear envelope

Chang Liu, Maho Takahashi, Yanping Li, Tara J. Dillon, Stefanie Kaech-Petrie, Philip Stork

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Epac1 (exchange protein directly activated by cyclic AMP [cAMP]) couples intracellular cAMP to the activation of Rap1, a Ras family GTPase that regulates cell adhesion, proliferation, and differentiation. Using mass spectrometry, we identified the small G protein Ran and Ran binding protein 2 (RanBP2) as potential binding partners of Epac1. Ran is a small G protein best known for its role in nuclear transport and can be found at the nuclear pore through its interaction with RanBP2. Here we demonstrate that Ran-GTP and Epac1 interact with each other in vivo and in vitro. This binding requires a previously uncharacterized Ras association (RA) domain in Epac1. Surprisingly, the interaction of Epac1 with Ran is necessary for the efficient activation of Rap1 by Epac1. We propose that Ran and RanBP2 anchor Epac1 to the nuclear pore, permitting cAMP signals to activate Rap1 at the nuclear envelope.

Original languageEnglish (US)
Pages (from-to)3956-3969
Number of pages14
JournalMolecular and Cellular Biology
Volume30
Issue number16
DOIs
StatePublished - Aug 2010

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Nuclear Envelope
Cyclic AMP
Nuclear Pore
Monomeric GTP-Binding Proteins
ras Proteins
Cell Nucleus Active Transport
Guanosine Triphosphate
Cell Adhesion
Cell Differentiation
Mass Spectrometry
Cell Proliferation
ran-binding protein 2
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

The interaction of Epac1 and ran promotes Rap1 activation at the nuclear envelope. / Liu, Chang; Takahashi, Maho; Li, Yanping; Dillon, Tara J.; Kaech-Petrie, Stefanie; Stork, Philip.

In: Molecular and Cellular Biology, Vol. 30, No. 16, 08.2010, p. 3956-3969.

Research output: Contribution to journalArticle

Liu, Chang ; Takahashi, Maho ; Li, Yanping ; Dillon, Tara J. ; Kaech-Petrie, Stefanie ; Stork, Philip. / The interaction of Epac1 and ran promotes Rap1 activation at the nuclear envelope. In: Molecular and Cellular Biology. 2010 ; Vol. 30, No. 16. pp. 3956-3969.
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