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Instability of GGL domain-containing RGS proteins in mice lacking the G protein beta -subunit G beta 5

RGS (regulator of G protein signaling) proteins containing the G protein gamma -like (GGL) domain (RGS6, RGS7, RGS9, and RGS11) interact with the fifth member of the G protein beta -subunit family, G beta 5. This interaction is necessary for the stability of both the RGS protein and for G beta 5. Co...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2003-05, Vol.100 (11), p.6604-6609
Main Authors: Chen, C-K, Eversole-Cire, P, Zhang, H, Mancino, V, Chen, Y-J, He, W, Wensel, T G, Simon, MI
Format: Article
Language:English
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Summary:RGS (regulator of G protein signaling) proteins containing the G protein gamma -like (GGL) domain (RGS6, RGS7, RGS9, and RGS11) interact with the fifth member of the G protein beta -subunit family, G beta 5. This interaction is necessary for the stability of both the RGS protein and for G beta 5. Consistent with this notion, we have found that elevation of RGS9-1 mRNA levels by transgene expression does not increase RGS9-1 protein level in the retina, suggesting that G beta 5 levels may be limiting. To examine further the interactions of G beta 5 and the GGL domain-containing RGS proteins, we inactivated the G beta 5 gene. We found that the levels of GGL domain-containing RGS proteins in retinas and in striatum are eliminated or reduced drastically, whereas the levels of G sub( gamma ) sub(2) and RGS4 proteins remain normal in the absence of G beta 5. The homozygous G beta 5 knockout (G beta 5 super(-) super(/) super(-)) mice derived from heterozygous knockout mating are runty and exhibit a high preweaning mortality rate. We concluded that complex formation between GGL domain-containing RGS proteins and the G beta 5 protein is necessary to maintain their mutual stability in vivo. Furthermore, in the absence of G beta 5 and all four RGS proteins that form protein complexes with G beta 5, the animals that survive into adulthood are viable and have no gross defects in brain or retinal morphology.
ISSN:0027-8424
DOI:10.1073/pnas.0631825100