E2F8 is a nonreceptor activator of heterotrimeric G proteins

Ian S Hagemann, Kirk D Narzinski, Thomas J Baranski


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.

View the full article: Full text PDF

How to cite: Hagemann, I.S., Narzinski, K.D. and Baranski, T.J. 2007. E2F8 is a nonreceptor activator of heterotrimeric G proteins. Journal of Molecular Signaling 2:3, DOI: http://dx.doi.org/10.1186/1750-2187-2-3

This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright is retained by the author(s).

This article has been peer reviewed (journal peer review policy).

Published on 30 March 2007.

ISSN: 1750-2187 | Published by Ubiquity Press | Creative Commons License This work is licensed under a Creative Commons License.