HECT domain-containing E3 ubiquitin ligase Nedd4 interacts with and ubiquitinates Sprouty2.

ABSTRACT: Sprouty (Spry) proteins are important regulators of receptor tyrosine kinase signaling in development and disease. Alterations in cellular Spry content have been associated with certain forms of cancers and also in cardiovascular diseases. Thus, understanding the mechanisms that regulate cellular Spry levels are important. Herein, we demonstrate that Spry1 and Spry2, but not Spry3 or Spry4, associate with the HECT domain family E3 ubiquitin ligase, Nedd4. The Spry2/Nedd4 association involves the WW domains of Nedd4 and requires phosphorylation of the Mnk2 kinase sites, Ser(112) and Ser(121), on Spry2. The phospho-Ser(112/121) region on Spry2 that binds WW domains of Nedd4 is a novel non-canonical WW domain binding region that does not contain Pro residues after phospho-Ser. Endogenous and

SUBMITTER: Edwin F 

PROVIDER: S-EPMC2804172 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature