RGS6, RGS7, RGS9, and RGS11 Stimulate GTPase Activity of Gi Family G-proteins with Differential Selectivity and Maximal Activity
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...
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Published in | The Journal of biological chemistry Vol. 278; no. 12; pp. 10087 - 10093 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
21.03.2003
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M211382200 |