N. Benbaruch et Y. Yarden, NEU DIFFERENTIATION FACTORS - A FAMILY OF ALTERNATIVELY SPLICED NEURONAL AND MESENCHYMAL FACTORS, Proceedings of the Society for Experimental Biology and Medicine, 206(3), 1994, pp. 221-227
The Neu proto-oncogene (also called ErbB-2 and HER-2) encodes a tyrosi
ne kinase transmembrane receptor homologous to the epidermal growth fa
ctor receptor (EGF-R). Overexpression, a point-mutation, and co-expres
sion with EGF-R activate the oncogenic potential of the Neu protein by
permanent coupling to signal transducing pathways. The search for lig
ands that elevate tyrosine phosphorylation of Neu led to the discovery
of a 44-kDa glycoprotein that acts either as a differentiation factor
or as a mitogen for mammary tumor cells. This protein, termed Neu dif
ferentiation factor (NDF), is derived from a transmembrane precursor t
hat contains an EGF-like motif and an immunoglobulin-like domain. Alte
rnative splicing generates a dozen NDF-related proteins that are expre
ssed in a variety of mesenchymal and neuronal tissues. This unpreceden
ted multiplicity raises the possibility that different isoforms fulfil
l distinct biological roles.