Sensory and motor neuron-derived factor. A novel heregulin variant highly expressed in sensory and motor neurons

The heregulin family of polypeptides arise as splice variants from a single gene and share a conserved epidermal growth factor (EGF)-like domain thought to be the major determinant of their biological activities. We report here the cloning of a novel member of this family, termed sensory and motor neuron-derived factor or SMDF, which is highly expressed in sensory and motor neurons in human and rodent species. It contains a C-terminal beta-type EGF-like domain and an unique N-terminal sequence which lacks an Ig-like domain and is distinct from all known heregulin variants. Mammalian cell-expressed SMDF activates tyrosine phosphorylation of a 185-kDa protein in cell lines expressing p185erbB2, indicating that it is biologically active. Analyses of expression patterns suggest that, unlike other heregulin variants, SMDF is expressed mainly in the nervous system. In situ hybridization signals with the unique SMDF sequence probe and with a probe to the conserved EGF-like domain are comparable, suggesting that SMDF is the predominant isoform expressed in sensory and motor neurons. Expression of SMDF is maintained in both adult motor neurons and dorsal root ganglion neurons. These findings suggest that SMDF may mediate biological responses such as Schwann cell proliferation and acetylcholine receptor induction in the peripheral nervous system.