Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/53943
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Nedd4 controls animal growth by regulating IGF-1 signaling |
Author: | Cao, X. Lill, N. Boase, N. Shi, P. Croucher, D. Shan, H. Qu, J. Sweezer, E. Place, T. Kirby, P. Daly, R. Kumar, S. Yang, B. |
Citation: | Science Signaling, 2008; 1(38):1-10 |
Publisher: | American Assoc Advancement Science |
Issue Date: | 2008 |
ISSN: | 1945-0877 1937-9145 |
Statement of Responsibility: | Xiao R. Cao, Nancy L. Lill, Natasha Boase, Peijun P. Shi, David R. Croucher, Hongbo Shan, Jing Qu, Eileen M. Sweezer, Trenton Place, Patricia A. Kirby, Roger J. Daly, Sharad Kumar, and Baoli Yang |
Abstract: | 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. |
Keywords: | Cells, Cultured Cell Membrane Animals Mice Mice, Mutant Strains Insulin Ubiquitin-Protein Ligases Receptor, IGF Type 1 Insulin-Like Growth Factor I Signal Transduction Phosphorylation GRB10 Adaptor Protein Endosomal Sorting Complexes Required for Transport Nedd4 Ubiquitin Protein Ligases |
DOI: | 10.1126/scisignal.1160940 |
Published version: | http://dx.doi.org/10.1126/scisignal.1160940 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.