Structure of Entire ErbB Receptor Ectodomains

A striking feature of ligand-induced dimers of sEGFR is that the dimer interface is mediated entirely by interreceptor contacts (Garrett et al, 

Receptor dimerization does not appear sufficient for signaling, however. Introduction of interreceptor disulfide bonds at different sites within the juxtamembrane region of ErbB receptors results in both active and inactive dimers (Burke et al, 1997). Requirement for a stereospecific dimer is also seen for cytokine receptors (Jiang and Hunter, 1999) and suggests that conformational information is transmitted across the plasma 

The active-like structure of HER2 provides a structural basis for its role as the preferred heterodimerization partner among ErbB receptors. HER2 does not adopt the autoinhibited conformation observed for EGFR and HERS but is instead poised to interact with any ErbB receptor that 

Interest in the mechanism by which HER2 homodimerization is disfavored is stimulated in part by a desire to understand how HER2 becomes activated when overexpressed (Brennan et al, 2000 Di Fiore et al, 1987). HER2 overexpression and activation contributes to the genesis and severity of human cancers (Blume-Jensen and Hunter, 2001 Holbro et al, 2003 Slamon et al, 1987 Tang and Lippman, 1998), and understanding HER2 

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