Neuroepithelial Cell Transforming Gene 1 (NET1)

By expression cloning and PCR of a neuroepithelioma cell line, followed by screening of a mammary epithelial cell line, Chan et al. (1996) obtained a cDNA encoding NET1. Sequence analysis predicted that the 601-amino acid protein has a DBL homology (DH) domain that is 21% similar to that of DBL, particularly in the leucine-rich region. The DH domain is a 240-amino acid region initially identified in DBL. DH domain proteins interact with members of the RAS superfamily of GTP-binding proteins. NET1 also possesses a pleckstrin-homology domain. Northern blot analysis revealed ubiquitous expression of major 3.0- and minor 2.4-kb NET1 transcripts, with highest levels in placenta. Functional analysis showed that NET1 induced morphologic alterations and conferred a malignant phenotype in vitro and in nude mice.