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Open Access Research article

E2F8 is a nonreceptor activator of heterotrimeric G proteins

Ian S Hagemann, Kirk D Narzinski and Thomas J Baranski*

Author Affiliations

Departments of Medicine and of Molecular Biology & Pharmacology, 660 S. Euclid Ave., Campus Box 8127, St. Louis, Missouri 63110, USA

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Journal of Molecular Signaling 2007, 2:3  doi:10.1186/1750-2187-2-3

Published: 30 March 2007

Abstract

Background

Heterotrimeric G proteins are important for numerous signaling events in eukaryotes, serving primarily to transduce signals that are initiated by G protein-coupled receptors. It has recently become clear that nonreceptor activators can regulate the level of heterotrimeric G protein signaling and, in some cases, drive cycles of receptor-independent G protein activation. In this study, we used a yeast expression cloning strategy to identify novel nonreceptor activators of heterotrimeric G proteins in a human adipocyte cDNA library.

Results

The human transcription factor E2F8 was found to activate heterotrimeric G proteins, suggesting a specific biological role for this recently described member of the E2F family. Epistasis studies showed that E2F8 acted at the level of G proteins and was specific for Gαi over Gpa1. E2F8 augmented receptor-driven signaling, but also activated G proteins in the absence of a receptor. The GTPase-activating protein RGS4 antagonized the effect of E2F8, showing that E2F8's effect on Gα involved nucleotide turnover. The entire E2F8 protein was required for full activity, but the majority of the signaling activity appeared to reside in the first 200 residues.

Conclusion

In yeast, E2F8 is a guanine nucleotide exchange factor (GEF) for the α subunit of heterotrimeric G proteins. The molecular mechanism and biological significance of this effect remain to be determined.