ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling

Abstract

activity, which leads to the phosphorylation of tyrosine residues in the intracellular domain of the receptors (van 1 Corresponding author der Geer et al., 1994). These serve as docking sites for a number of SH2-and PTB-domain containing proteins We have analyzed ErbB receptor interplay induced by (Kavanaugh and Williams, 1994;Cohen,G.B. et al., 1995 Riese et al. 1996); neu ErbB-2, suggesting that ErbB-2 has a role in the lateral differentiation factors (NDFs)/heregulins (Peles and transmission of signals between other ErbB receptors. Yarden, 1993), which are ligands of ErbB-3 and ErbB-4 Finally, ErbB-1 activated by all EGF-related peptides (Plowman et al., 1993b;, the (EGF, HB-EGF, BTC and NDF) couples to SHC, respective low and high affinity receptors (Tzahar et al., whereas only ErbB-1 activated by its own ligands 1994). associates with and phosphorylates Cbl. These results By binding to the ECD of their respective receptors, provide the first biochemical evidence that a given ErbB EGF-related peptides induce not only receptor homodimers receptor has distinct signaling properties depending on but also heterodimers. Consequently, although none of its dimerization.these peptides directly bind ErbB-2, all of them induce its

Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation

“…ErbB2 is the preferred heterodimer partner of activated EGFR family members (Graus-Porta et al, 1997;Tzahar et al, 1996), and, when mutated, can inactivate other ErbB-family receptors (Qian et al, 1994). Therefore, we cannot rule out the possibility that in addition to inhibiting ErbB2 signaling, ErbB2DIC inactivates signaling by other members of the EGFR-family.…”

“…This is mediated by induction of EGFR/ErbB2 heterodimers (Spivak-Kroizman et al, 1992;Wada et al, 1990). Although each ligand-activated EGFR-family member can form a signaling dimer with most other members of this receptor family, ErbB2 is the preferred heterodimer partner (Graus-Porta et al, 1997;Tzahar et al, 1996). Moreover, ligand stimulated receptors compete for dimer formation with ErbB2 Karunagaran et al, 1996).…”

Prognostic value of the ubiquitin ligase carboxyl terminus of the Hsc70‐interacting protein in postmenopausal breast cancer

“…HER2 is a member of the ErbB‐protein family and acts in a signaling network in the cellular membrane 14. HER2‐containing dimers have been shown to enhance downstream signaling 14, 15. The mechanism underlying the down‐regulated expression of HER2 signaling involves the removal of receptors from the cell surface in the course of initial ligand‐induced endocytosis and subsequent sorting to the lysosome for degradation through ubiquitination 16.…”

Intratumoral administration of an adenovirus expressing a kinase dead form of ErbB-2 inhibits tumor growth

“…ErbB-2 receptor signaling involves homo-and heterodimerization with ErbB family members leading to kinase activation, trans-tyrosine phosphorylation and signal transduction. 21,22 When inactive forms of ErbB-2 binding partners are co-expressed with ErbB-2, dimer formation between the two leads to receptor inactivation. Previously the expression of inactive ErbB-2 has been demonstrated to inhibit activity of ErbB-2 and reverse ErbB-2 mediated transformation in vitro.…”

“…20 ErbB-2 receptor signaling involves ligand binding, homo-and heterodimerization with other ErbB family members, such as ErbB-3, leading to kinase activation, trans-tyrosine phosphorylation and signal transduction. 21,22 When kinase dead forms of ErbB-2 are coexpressed with ErbB-2, the kinase dead ErbB-2 acts in a dominant negative fashion. Dimer formation between the two leads to receptor inactivation.…”