The deaf and the dumb: The biology of ErbB-2 and ErbB-3

Ami Citri, Kochupurakkal Bose Skaria, Yosef Yarden*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

498 Scopus citations


ErbB-2 (also called HER2/neu) and ErbB-3 are closely related to the epidermal growth factor receptor (EGFR/ErbB-1), but unlike EGFR, ErbB-2 is a ligandless receptor, whereas ErbB-3 lacks tyrosine kinase activity. Hence, both ErbB-2 and ErbB-3 are active only in the context of ErbB heterodimers, and ErbB-2·ErbB-3 heterodimers, which are driven by neuregulin ligands, are the most prevalent and potent complexes. These stringently controlled heterodimers are repeatedly employed throughout embryonic development and dictate the establishment of several cell lineages through mesenchyme-epithelial inductive processes and the interactions of neurons with muscle, glia, and Schwann cells. Likewise, the potent combination of signaling pathways engaged by the heterodimers drives an aggressive phenotype of tumors of secretory epithelia, including breast and lung cancers. This review highlights recent structural insights into the mechanism of ligand-induced heterodimer formation, and concentrates on signaling pathways employed by ErbB-2 and ErbB-3 in normal and in malignant cells.

Original languageAmerican English
Pages (from-to)54-65
Number of pages12
JournalExperimental Cell Research
Issue number1
StatePublished - 10 Mar 2003
Externally publishedYes

Bibliographical note

Funding Information:
We thank Sarah Bacus, Jorma Isola, and Mark Sliwkowski for insightful discussions. Our laboratory is supported by grants from the National Cancer Institute, the U.S. Army, the European Commission, and the Israel Academy of Sciences and Humanities.


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