| Grb 10 coimmunoprecipitates with the IGF IR and endogenous Nedd 4 in p6 / Grb10 cells , suggesting the presence of a Grb10 / Nedd4 / IGF IR complex . ^^^ Ubiquitination of the IGF IR in p6 / Grb10 cells is severely impaired by overexpression of a catalytically inactive Nedd 4 mutant ( Nedd 4 CS ) , which also stabilizes the receptor . ^^^ Likewise , overexpression of a Grb 10 mutant lacking the Src homology 2 ( SH 2 ) domain impaired ubiquitination of the IGF IR in parental p 6 and p6 / Grb10 cells , indicating that Grb 10 binding to Nedd 4 is critical for ubiquitination of the receptor . ^^^ These results suggest a role for the Grb10 / Nedd4 complex in regulating ubiquitination and stability of the IGF IR , and they suggest that Grb 10 serves as an adapter to form a bridge between Nedd 4 and the IGF IR . ^^^ |