NEU DIFFERENTIATION FACTORS - A FAMILY OF ALTERNATIVELY SPLICED NEURONAL AND MESENCHYMAL FACTORS

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.