Neuregulins and Their Receptors: A Versatile Signaling Module in Organogenesis and Oncogenesis

yet to be identified. Like their mammalian counterparts, There has been rapid growth in our understanding of the invertebrate ErbB receptors also signal primarily neuregulins (NRGs), a large group of structurally related through the Ras-Raf-MAP-kinase pathway. In both inpolypeptide factors, and their receptors, four transmemvertebrates and mammals, the signaling module is necbrane tyrosine kinases of the ErbB family. This new essary for development of multiple and seemingly unreknowledge reveals a complex signaling system, used in lated cell lineages and organs, and its requirement different tissues to regulate cell survival, proliferation, coincides with more than one developmental phase. and differentiation. Only 5 years ago, independent efAnother lesson that is mirrored in mammals is the tightly forts to identify activities responsible for stimulating controlled availability of the ligands, whose range of Neu/ErbB-2 phosphorylation, Schwann cell proliferation, action is relatively short; the synthesizing cell and the and acetylcholine receptor synthesis resulted in the responsive tissue are juxtaposed or only a few cell layers striking discovery that the peptide factors, Neu differenapart. tiation factor (NDF/heregulin), glial growth factor (GGF),