CHARACTERIZATION OF A NEUREGULIN-RELATED GENE, DON-1, THAT IS HIGHLY EXPRESSED IN RESTRICTED REGIONS OF THE CEREBELLUM AND HIPPOCAMPUS

Members of the epidermal growth factor family of receptors have long b een implicated in the pathogenesis of various tumors, and more recentl y, apparent roles in the developing heart and nervous system have been described, Numerous ligands that activate these receptors have been i solated, We report here on the cloning and initial characterization of a second ligand for the erbB family of receptors, This factor, which we have termed Don-l (divergent of neuregulin 1), has structural simil arity with the neuregulins, We have isolated four splice variants, two each from human and mouse, and have shown that they are capable of in ducing tyrosine phosphorylation of erbB3, erbB4, and erbB2. In contras t to those of neuregulin, high levels of expression of Don-1 are restr icted to the cerebellum and dentate gyrus in the adult brain and to fe tal tissues.