Mutation of the c-Cbl TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein.

@article{Peschard2001MutationOT,
  title={Mutation of the c-Cbl TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein.},
  author={Pascal Peschard and T M Fournier and Louie Lamorte and Monica A Naujokas and Hamid Band and Wallace Y Langdon and Morag Park},
  journal={Molecular cell},
  year={2001},
  volume={8 5},
  pages={995-1004}
}
The c-Cbl protooncogene is a negative regulator for several receptor tyrosine kinases (RTKs) through its ability to promote their polyubiquitination. Hence, uncoupling c-Cbl from RTKs may lead to their deregulation. In testing this, we show that c-Cbl promotes ubiquitination of the Met RTK. This requires the c-Cbl tyrosine kinase binding (TKB) domain and a juxtamembrane tyrosine residue on Met. This tyrosine provides a direct binding site for the c-Cbl TKB domain, and is absent in the… CONTINUE READING