Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP

Johan de Rooij, Fried J. T. Zwartkruis, Mark H. G. Verheijen, Robbert H. Cool, Sebastian M. B. Nijman, Alfred Wittinghofer and Johannes L. Bos ()
Additional contact information
Johan de Rooij: Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University
Fried J. T. Zwartkruis: Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University
Mark H. G. Verheijen: Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University
Robbert H. Cool: Max Planck Institute für Moleculare Physiologie
Sebastian M. B. Nijman: Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University
Alfred Wittinghofer: Max Planck Institute für Moleculare Physiologie
Johannes L. Bos: Laboratory for Physiological Chemistry and Centre for Biomedical Genetics, Utrecht University

Nature, 1998, vol. 396, issue 6710, 474-477

Abstract: Abstract Rap1 is a small, Ras-like GTPase that was first identified as a protein that could suppress the oncogenic transformation of cells by Ras1. Rap1 is activated by several extracellular stimuli2,3,4,5,6,7 and may be involved in cellular processes such as cell proliferation8, cell differentiation4, T-cell anergy2 and platelet activation7. At least three different second messengers, namely diacylglycerol, calcium and cyclic AMP5,6,7,8,9 are able to activate Rap1 by promoting its release of the guanine nucleotide GDP and its binding to GTP. Here we report that activation of Rap1 by forskolin and cAMP occurs independently of protein kinase A (also known as cAMP-activated protein kinase). We have cloned the gene encoding a guanine-nucleotide-exchange factor (GEF) which we have named Epac (exchange protein directly activated by cAMP). This protein contains a cAMP-binding site and a domain that is homologous to domains of known GEFs for Ras and Rap1. Epac binds cAMP in vitro and exhibits in vivo and in vitro GEF activity towards Rap1. cAMP strongly induces the GEF activity of Epac towards Rap1 both in vivo and in vitro. We conclude that Epac is a GEF for Rap1 that is regulated directly by cAMP and that Epac is a new target protein for cAMP.

Date: 1998
References: Add references at CitEc
Citations: View citations in EconPapers (6)

Downloads: (external link)
https://www.nature.com/articles/24884 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:396:y:1998:i:6710:d:10.1038_24884

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/24884

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().