Neu and its ligands: from an oncogene to neural factors

Bioessays. 1993 Dec;15(12):815-24. doi: 10.1002/bies.950151207.


Transmembrane receptor tyrosine kinases that bind to peptide factors transmit essential growth and differentiation signals. A growing list of orphan receptors, of which some are oncogenic, holds the promise that many unknown ligands may be discovered by tracking the corresponding surface molecules. The neu gene (also called erbB-2 and HER-2) encodes such a receptor tyrosine kinase whose oncogenic potential is released in the developing rodent nervous system through a point mutation. Amplification and overexpression of neu are thought to contribute to malignancy of certain human adenocarcinomas. The search for soluble factors that interact with the Neu receptor led to the discovery of a 44 kDa glycoprotein that induces phenotypic differentiation of cultured mammary tumor cells to growth-arrested and milk-producing cells. The Neu differentiation factor (NDF or heregulin), however, also acts as a mitogen for epithelial, Schwann and glial cells. Multiple forms of the factor are produced by alternative splicing and their expression is confined predominantly to the central and to the peripheral nervous systems. One identified neuronal function of this family of polypeptides is to control the formation of neuromuscular junctions, but their physiological role in secretory epithelia is still unknown. Other open questions relate to the transmembrane topology of various precursors, the identity of a putative coreceptor, the possible existence of additional ligands of Neu and the functional significance of the interaction between Neu and at least three highly related receptor tyrosine kinases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Transformation, Neoplastic / genetics
  • ErbB Receptors / chemistry
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / metabolism
  • Humans
  • Ligands
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Multigene Family
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplasms, Experimental / genetics
  • Neuregulins
  • Oncogenes*
  • Point Mutation
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases* / genetics
  • Protein-Tyrosine Kinases* / metabolism
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogenes
  • Rats
  • Receptor, ErbB-2
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction


  • Glycoproteins
  • Ligands
  • Neuregulins
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2