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

There has been rapid growth in our understanding of neuregulins (NRGs), a large group of structurally related polypeptide factors, and their receptors, four transmembrane tyrosine kinases of the ErbB family. This new knowledge reveals a complex signaling system, used in different tissues to regulate cell survival, proliferation, and differentiation. Only 5 years ago, independent efforts to identify activities responsible for stimulating Neu/ErbB-2 phosphorylation, Schwann cell proliferation, and acetylcholine receptor synthesis resulted in the striking discovery that the peptide factors, Neu differentiation factor (NDF/heregulin), glial growth factor (GGF), and acetylcholine receptor inducing activity (ARIA) were the products of the same gene. The name neuregulin, originally introduced by Mark Marchionni, represents a composite of the initial names and recognizes the importance of these factors in the nervous system. Intensive efforts have now clarified not only an enormous functional diversity of the NRG-ErbB signaling network, but also its role in midgestation organogenesis as a key determinant in differentiation of several cell lineages (Figure 1). Instructive illustrations of this diversity were provided by presentations at a recent workshop organized in the Banbury Center at the Cold Spring Harbor Laboratory by Mark A. Marchionni (Cambridge NeuroScience) and Greg Lemke (Salk Institute, La Jolla, CA) on “Neuregulins and Neuregulin Receptors.”