Date of Award
2006
Degree Type
Thesis
Degree Name
Master of Science
Program
Pharmacology and Toxicology
Supervisor
Dr. P. Chidiac
Second Advisor
Dr. D. Bai
Third Advisor
Dr. S. Sims
Abstract
Regulator of G protein signalling (RGS) proteins are primarily known to attenuate G protein function within G protein-coupled receptor (GPCR) signalling pathways, however they can interact with additional proteins. We identified an interaction between RGS proteins (RGS4, RGS5, RGS16) and the multifunctional protein 14-3-3. Two isoforms, 14-3-3β and 14-3-3ε, interact with all three purified RGS proteins. Data from in vitro steady state GTP hydrolysis assays show that 14-3-3 inhibits the GTPase activity of RGS4 and RGSI6, but has no appreciable effect on RGS5. Furthermore in a competitive pull-down experiment, 14-3-3ε competes with Gαo for RGS4 but not for RGS5. Thus 143-3 proteins may prevent RGS from interacting with Ga and ultimately prolong signalling. Tyrosine 167 within the conserved 14-3-3 binding motif does not play a significant role in RGS inhibition by 14-3-3. In conclusion, 14-3-3 proteins appear to indirectly promote GPCR signalling via their inhibitory effects on RGS function.
Recommended Citation
Abramow-Newerly, Maria, "MODULATION OF REGULATOR OF G PROTEIN SIGNALLING (RGS) FUNCTION BY 14-3-3 PROTEINS" (2006). Digitized Theses. 4983.
https://ir.lib.uwo.ca/digitizedtheses/4983