title: Regulation of RGS5 GAP activity by GPSM3.
abstract: 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.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
authors.forename: Peishen
authors.initials: P
authors.lastname: Zhao
authors.forename: Peter
authors.initials: P
authors.lastname: Chidiac
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D003412:Cricetulus; D020555:GTP-Binding Protein Regulators / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D020710:RGS Proteins / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000502:physiology
chemical_list: D020555:GTP-Binding Protein Regulators; D020730:Guanine Nucleotide Dissociation Inhibitors; D020710:RGS Proteins; C491348:Rgs5 protein, rat; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins
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