RGS6, RGS7, RGS9, and RGS11 Stimulate GTPase Activity of Gi Family G-proteins with Differential Selectivity and Maximal Activity

• Published in: The Journal of biological chemistry Vol. 278; no. 12; pp. 10087 - 10093
• Main Authors: Hooks, Shelley B, Waldo, Gary L, Corbitt, James, Bodor, Erik T, Krumins, Andrejs M, Harden, T Kendall
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 21.03.2003
• Subjects: Animals; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; GTP-Binding Proteins - physiology; GTPase-Activating Proteins - physiology; Guanosine Triphosphate - metabolism; Heterotrimeric GTP-Binding Proteins - chemistry; Heterotrimeric GTP-Binding Proteins - physiology; Hydrolysis; RGS Proteins - physiology; Spodoptera
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M211382200

Regulator of G-protein signaling (RGS) proteins are GTPase activating proteins (GAPs) of heterotrimeric G-proteins that alter the amplitude and kinetics of receptor-promoted signaling. In this study we defined the G-protein α-subunit selectivity of purified Sf9 cell-derived R7 proteins, a subfamily of RGS proteins (RGS6, -7, -9, and -11) containing a Gγ-like (GGL) domain that mediates dimeric interaction with Gβ 5 . Gβ 5 /R7 dimers stimulated steady state GTPase activity of Gα-subunits of the G i family, but not of Gα q or Gα 11 , when added to proteoliposomes containing M2 or M1 muscarinic receptor-coupled G-protein heterotrimers. Concentration effect curves of the Gβ 5 /R7 proteins revealed differences in potencies and efficacies toward Gα-subunits of the G i family. Although all four Gβ 5 /R7 proteins exhibited similar potencies toward Gα o , Gβ 5 /RGS9 and Gβ 5 /RGS11 were more potent GAPs of Gα i1 , Gα i2 , and Gα i3 than were Gβ 5 /RGS6 and Gβ 5 /RGS7. The maximal GAP activity exhibited by Gβ 5 /RGS11 was 2- to 4-fold higher than that of Gβ 5 /RGS7 and Gβ 5 /RGS9, with Gβ 5 /RGS6 exhibiting an intermediate maximal GAP activity. Moreover, the less efficacious Gβ 5 /RGS7 and Gβ 5 /RGS9 inhibited Gβ 5 /RGS11-stimulated GTPase activity of Gα o . Therefore, R7 family RGS proteins are G i family-selective GAPs with potentially important differences in activities.