ErbB receptors and EGF-like ligands: Cell lineage determination and oncogenesis through combinatorial signaling

Ronit Pinkas-Kramarski, Iris Alroy, Yosef Yarden*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

The ErbB/HER family of transmembrane receptor tyrosine kinases includes four members that bind more than two dozens ligands sharing an epidermal growth factor- (EGF)3 like motif. This family plays a pivotal role in cell lineage determination in a variety of tissues, including mesenchyme-epithelial inductive processes and the interactions between neurons and muscle, glia and Schwann cells. Certain ligands and receptors of the family, especially the ErbB-2 receptor tyrosine kinase, contribute to a relatively virulent phenotype of some human tumors; most notable are carcinomas of secretory epithelia. This large variety of biological signals is generated through a combinatorial network of signal transduction in which different ErbB ligands are apparently capable of stabilizing discrete homo- and heterodimeric receptor complexes, each coupled to a specific set of cytoplasmic signaling proteins. Because each receptor is unique in terms of catalytic activity, cellular routing and transmodulation, the resulting network allows not only an enormous potential for signal diversification but also fine tuning and stringent control of cellular functions. ErbB-2 emerges as a master coordinator of the network, prolonging and amplifying signaling by decelerating the dissociation rates of its heterologous ligands. Thus, the tumorigenic action of ErbB-2 may be attributed to its ability to act as a shared signaling subunit, rather than by functioning as a bone fide receptor.

Original languageEnglish
Pages (from-to)97-107
Number of pages11
JournalJournal of Mammary Gland Biology and Neoplasia
Volume2
Issue number2
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • Cancer
  • Growth factor
  • Receptor
  • Signal transduction
  • Tyrosine kinase

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