Nov 10, 2021 · In a structure of the oncogenic extracellular domain mutant HER2(S310F), we observe a compensatory interaction with the HER3 dimerization arm that stabilizes the dimerization interface.

Upon ligand binding, the dimerization partner’s kinase domain trans-phosphorylates the tyrosine residues in the C-terminal tail of HER3 . The preferable dimerization partners for HER3 are EGFR and HER2, followed by lower affinity to HER4 .

Mar 14, 2025 · Despite having only weak intrinsic kinase activity, HER3 can contribute to oncogenic signalling via ligand-induced heterodimerization with other HER family members. Evidence indicates that HER3...

Dec 2, 2014 · To determine the structural basis for HER3 signaling through heterodimerization with a catalytically active HER family member, we solved the crystal structure of the heterodimeric complex formed by the isolated kinase domains of EGFR and HER3.

Jun 24, 2021 · HER3 E928G enhanced dimerization affinities over HER3 WT in all cases (Figures 2C and S3B). We tested the hypothesis that HER2 missense mutants increase the stability of the KD active conformation using steered MD and umbrella sampling (US) simulations.

The preferred dimerization partner of 62 HER2 is HER3, which binds growth factors from the neuregulin (NRG) family1-3. Like HER2, 63 HER3 is an obligate heterodimer partner, because it has a catalytically impaired kinase domain 64 (a pseudokinase) and cannot support its own phosphorylation14,15.

Feb 28, 2010 · The recent landmark study revealing a highly unique mechanism underlying kinase domain activation in the HER family now finally identifies the potential functions of a catalytically inactive kinase domain such as that of HER3. In the HER family, dimerization of the kinase domains occurs in an asymmetric configuration leading to the allosteric ...

HER2-HER3 dimerization is associated with metastatic relapse in breast cancer patients. Within the whole TMA cohort (n = 218), in univariate Cox survival models, HER2 status was significantly associated with metastasis-free survival at 5 years (Figure 5A).

May 1, 2018 · Here, we show that lapatinib, an ATP-competitive inhibitor of HER2, is able to induce proliferation cooperatively with the HER3 ligand neuregulin. This counterintuitive synergy between inhibitor and growth factor depends on their ability to promote atypical HER2-HER3 heterodimerisation.

Our 3.5Å structure of the HER2-S310F/HER3/NRG1β/trastuzumab Fragment antigen binding (Fab) complex reveals that the receptor dimer undergoes a conformational change to accommodate trastuzumab. Thus, like oncogenic mutations, therapeutics exploit the intrinsic dynamics of the HER2/HER3 heterodimer.