caa a22 4500 606234535 CHVBK 20210128101237.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s11010-015-2393-3 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2393-3 Regulation of RGS5 GAP activity by GPSM3 [Elektronische Daten] [Peishen Zhao, Peter Chidiac] Heterotrimeric G protein signaling is limited by intracellular proteins that impede the binding of or accelerate the hydrolysis of the activating nucleotide GTP, exemplified respectively by the G protein-signaling modifier (GPSM) and regulator of G protein-signaling (RGS) families of proteins. Little is known about how members of these groups of proteins might influence the impact of the other on G protein activity. In the present study, we have identified novel binding and functional interactions between GPSM3 (also known as activator of G protein-signaling 4 (AGS4) or G18) and RGS5, both of which were found to be expressed in primary rat aortic smooth muscle cell cultures. The binding of GPSM3 to RGS5 appears to be selective as no interactions were detected with other RGS proteins tested. In solution-based experiments, the addition of GPSM3 was found to enhance the ability of RGS5 to accelerate GTP hydrolysis by Gαi1 but not that of RGS4. In membrane-based assays utilizing M2 muscarinic receptor-activated Gαi1, GPSM3 decreased the rate of GTP hydrolysis in the presence of RGS4 but not RGS5, suggesting that the enhancement of RGS5 activity by GPSM3 is maintained under these conditions and/or that the binding of RGS5 to GPSM3 impedes its inhibitory effect on GTP turnover. Overall these findings show that it is possible for GPSM and RGS proteins to bind to one another to produce distinct regulatory effects on heterotrimeric G protein activity. Springer Science+Business Media New York, 2015 GPSM proteins nationallicence RGS proteins nationallicence G protein activation nationallicence GTPase activity nationallicence GPSM : G protein-signaling modifier nationallicence RGS : Regulator of G protein signaling nationallicence GPCR : G protein-coupled receptor nationallicence GAP : GTPase-accelerating protein nationallicence GEF : Guanine nucleotide exchange factor nationallicence VSMC : Vascular smooth muscle cell nationallicence Zhao Peishen Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, VIC, Australia aut Chidiac Peter Department of Physiology and Pharmacology, University of Western Ontario, N6A 5C1, London, ON, Canada aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 33-40 0300-8177 405:1-2<33 2015 405 11010 https://doi.org/10.1007/s11010-015-2393-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 brief-communication jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2393-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhao Peishen Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, 3052, Parkville, VIC, Australia aut NATIONALLICENCE 700 1- Chidiac Peter Department of Physiology and Pharmacology, University of Western Ontario, N6A 5C1, London, ON, Canada aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 33-40 0300-8177 405:1-2<33 2015 405 11010