Research ArticleDevelopmental Biology

Nedd4 Controls Animal Growth by Regulating IGF-1 Signaling

Science Signaling  23 Sep 2008:
Vol. 1, Issue 38, pp. ra5
DOI: 10.1126/scisignal.1160940

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A Growth-Promoting Ubiquitin Ligase

Genetic knockout of the ubiquitin ligase Nedd4 decreases insulin-like growth factor 1 (IGF-1) and insulin signaling and causes delayed embryonic development, reduced growth and body weight, and neonatal lethality. Elevated Grb10 in the Nedd4-deficient cells appears to cause mislocalization of the IGF-1 receptor and prevent receptor signaling at the plasma membrane. Thus, by regulating the abundance of Grb10, a negative regulator of IGF-1 and insulin signaling, Nedd4 positively influences growth.

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