ERBB2 forms heterodimers with ligand-activated ERBB receptors: EGFR, ERBB3 and ERBB4

Stable Identifier
Reaction [dissociation]
Homo sapiens
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ERBB2, which does not bind any known ligand, is activated through formation of a heterodimer with another ligand-activated ERBB family member. ERBB2 heterodimerization partners are EGF-stimulated EGFR (Wada et al. 1990, Karunagaran et al. 1996), ERBB3 stimulated by neuregulins NRG1 or NRG2 (Pinkas-Kramarski et al. 1996), and ERBB4 stimulated by neuregulins or EGF-like ligands (Li et al. 2007). In the process of dimerization, ERBB2 dissociates from chaperone proteins HSP90 and CDC37 (Xu et al 2001, Citri et al. 2004). Activated ERBB2 also dissociates from ERBB2IP, the protein responsible for proper localization of ERBB2 to basolateral membranes of epithelial cells (Borg et al. 2000).

Literature References
PubMed ID Title Journal Year
8665853 Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions

Ratzkin, BJ, Klapper, L, Levkowitz, G, Seger, R, Alroy, I, Waterman, H, Sela, M, Yarden, Y, Lavi, S, Pinkas-Kramarski, R, Soussan, L

EMBO J 1996
8617201 ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer

Beerli, RR, Ratzkin, BJ, Seger, R, Karunagaran, D, Chen, X, Hynes, NE, Graus-Porta, D, Tzahar, E, Yarden, Y

EMBO J 1996
15568014 Hsp90 restrains ErbB-2/HER2 signalling by limiting heterodimer formation

Gan, J, Szollosi, J, Yarden, Y, Vereb, G, Mosesson, Y, Citri, A

EMBO Rep 2004
11071886 Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90

Mimnaugh, E, Rosser, MF, Neckers, LM, Yarden, Y, Nicchitta, C, Marcu, M, Xu, W

J Biol Chem 2001
16978839 Neuregulin-1 only induces trans-phosphorylation between ErbB receptor heterodimer partners

Mei, Y, Li, Z, Zhou, M, Liu, X

Cell Signal 2007
15643424 Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex

Mimnaugh, E, Yuan, X, Xiang, Z, Neckers, LM, Marcu, M, Xu, W

Nat Struct Mol Biol 2005
10878805 ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor

Saito, H, Jaulin-Bastard, F, Borg, JP, Adelaide, J, Le Bivic, A, Marchetto, S, Birnbaum, D, Fournier, E, Margolis, B, Ollendorff, V

Nat Cell Biol 2000
1973074 Intermolecular association of the p185neu protein and EGF receptor modulates EGF receptor function

Greene, MI, Wada, T, Qian, XL

Cell 1990
This event is regulated