Nedd4 Controls Animal Growth by Regulating IGF-1 Signaling

被引：133

作者：

Cao, Xiao R. ^{[2
]}

Lill, Nancy L. ^{[2
]}

Boase, Natasha ^{[1
]}

Shi, Peijun P. ^{[2
]}

Croucher, David R. ^{[3
]}

Shan, Hongbo ^{[2
]}

Qu, Jing ^{[2
]}

Sweezer, Eileen M. ^{[2
]}

Place, Trenton ^{[2
]}

Kirby, Patricia A. ^{[2
]}

Daly, Roger J. ^{[3
]}

Kumar, Sharad ^{[1
,4
]}

Yang, Baoli ^{[2
]}

机构：

[1] Inst Med & Vet Sci, Hanson Inst, Adelaide, SA 5000, Australia

[2] Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USA

[3] Garvan Inst Med Res, Sydney, NSW 2010, Australia

[4] Univ Adelaide, Dept Med, Adelaide, SA 5005, Australia

来源：

SCIENCE SIGNALING | 2008年 / 1卷 / 38期

关键词：

D O I：

10.1126/scisignal.1160940

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The ubiquitin ligase Nedd4 has been proposed to regulate a number of signaling pathways, but its physiological role in mammals has not been characterized. Here we present an analysis of Nedd4-null mice to show that loss of Nedd4 results in reduced insulin-like growth factor 1 (IGF-1) and insulin signaling, delayed embryonic development, reduced growth and body weight, and neonatal lethality. In mouse embryonic fibroblasts, mitogenic activity was reduced, the abundance of the adaptor protein Grb10 was increased, and the IGF-1 receptor, which is normally present on the plasma membrane, was mislocalized. However, surface expression of IGF-1 receptor was restored in homozygous mutant mouse embryonic fibroblasts after knockdown of Grb10, and Nedd4(-/-) lethality was rescued by maternal inheritance of a disrupted Grb10 allele. Thus, in vivo, Nedd4 appears to positively control IGF-1 and insulin signaling partly through the regulation of Grb10 function.

引用

页数：10

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