期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：11
页码：6604-6609
DOI：10.1073/pnas.0631825100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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{gamma}2 and RGS4 proteins remain normal in the absence of G{beta}5. The homozygous G{beta}5 knockout (G{beta}5-/-) 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.
