Send to

Choose Destination
See comment in PubMed Commons below
Biochem J. 2003 Jun 15;372(Pt 3):897-903.

The soluble ectodomain of RetC634Y inhibits both the wild-type and the constitutively active Ret.

Author information

Istituto per l'Endocrinologia e l'Oncologia Sperimentale del CNR G. Salvatore, via Pansini 5, 80131 Napoli, Italy.


Substitution of Cys-634 in the extracellular domain of the Ret tyrosine kinase receptor causes its dimerization and activation of its transforming potential. To gain further insight into the molecular basis leading to Ret activation we purified a mutant protein consisting of the entire ectodomain of the Ret carrying a Cys-634-->Tyr substitution (EC-Ret(C634Y)). The protein is glycosylated, like the native one, and is biologically active. By using an in vitro cell system we show that EC-Ret(C634Y) inhibits the membrane-bound receptor Ret(C634Y), interfering with its dimerization. Furthermore, we demonstrate that EC-Ret(C634Y) competes with the wild-type Ret receptor for ligand binding. The results presented support the notion of the possible involvment of glial cell line-derived neurotrophic factor (GDNF) with multiple endocrine neoplasia type 2A (MEN2A) tumours, and describe a useful tool for generating molecular mimetics directed towards specific mutations of the ret oncogene.

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center