The authors declare that they have no conflict of interest.
The Ras-binding domain region of RGS14 regulates its functional interactions with heterotrimeric G proteins†
Article first published online: 16 APR 2013
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 6, pages 1414–1423, June 2013
How to Cite
Zhao, P., Nunn, C., Ramineni, S., Hepler, J. R. and Chidiac, P. (2013), The Ras-binding domain region of RGS14 regulates its functional interactions with heterotrimeric G proteins. J. Cell. Biochem., 114: 1414–1423. doi: 10.1002/jcb.24483
- Issue published online: 16 APR 2013
- Article first published online: 16 APR 2013
- Accepted manuscript online: 17 DEC 2012 08:21AM EST
- Manuscript Accepted: 6 DEC 2012
- Manuscript Received: 26 MAR 2012
- Natural Sciences and Engineering Research Council of Canada
- Canadian Institutes of Health Research
- US National Institutes of Health. Grant Numbers: R01-NS37112, R01-NS049195
- Career Investigator Award from the Heart and Stroke Foundation of Canada
- RGS PROTEINS;
- GAP ACTIVITY;
- GDI ACTIVITY;
- GAP-ENHANCING ACTIVITY;
- Ras-BINDING DOMAIN;
- INTRAMOLECULAR INTERACTION
RGS14 is a 60 kDa protein that contains a regulator of G protein signaling (RGS) domain near its N-terminus, a central region containing a pair of tandem Ras-binding domains (RBD), and a GPSM (G protein signaling modulator) domain (a.k.a. Gi/o-Loco binding [GoLoco] motif) near its C-terminus. The RGS domain of RGS14 exhibits GTPase accelerating protein (GAP) activity toward Gαi/o proteins, while its GPSM domain acts as a guanine nucleotide dissociation inhibitor (GDI) on Gαi1 and Gαi3. In the current study, we investigate the contribution of different domains of RGS14 to its biochemical functions. Here we show that the full-length protein has a greater GTPase activating activity but a weaker inhibition of nucleotide dissociation relative to its isolated RGS and GPSM regions, respectively. Our data suggest that these differences may be attributable to an inter-domain interaction within RGS14 that promotes the activity of the RGS domain, but simultaneously inhibits the activity of the GPSM domain. The RBD region seems to play an essential role in this regulatory activity. Moreover, this region of RGS14 is also able to bind to members of the B/R4 subfamily of RGS proteins and enhance their effects on GPCR-activated Gi/o proteins. Overall, our results suggest a mechanism wherein the RBD region associates with the RGS domain region, producing an intramolecular interaction within RGS14 that enhances the GTPase activating function of its RGS domain while disfavoring the negative effect of its GPSM domain on nucleotide dissociation. J. Cell. Biochem. 114: 1414–1423, 2013. © 2012 Wiley Periodicals, Inc.