The Dipole Potential Modifies the Clustering and Ligand Binding Affinity of ErbB Proteins and Their Signaling Efficiency

T. Kovács, G. Batta, Tímea Hajdu, Ágnes Szabó, Tímea Váradi, Florina Zákány, István Csomós, J. Szöllősi, Peter Nagy

Research output: Contribution to journalArticle

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Abstract

Although activation of the ErbB family of receptor tyrosine kinases (ErbB1-4) is driven by oligomerization mediated by intermolecular interactions between the extracellular, the kinase and the transmembrane domains, the transmembrane domain has been largely neglected in this regard. The largest contributor to the intramembrane electric field, the dipole potential, alters the conformation of transmembrane peptides, but its effect on ErbB proteins is unknown. Here, we show by Förster resonance energy transfer (FRET) and number and brightness (N&B) experiments that the epidermal growth factor (EGF)-induced increase in the homoassociation of ErbB1 and ErbB2 and their heteroassociation are augmented by increasing the dipole potential. These effects were even more pronounced for ErbB2 harboring an activating Val → Glu mutation in the transmembrane domain (NeuT). The signaling capacity of ErbB1 and ErbB2 was also correlated with the dipole potential. Since the dipole potential decreased the affinity of EGF to ErbB1, the augmented growth factor-induced effects at an elevated dipole potential were actually induced at lower receptor occupancy. We conclude that the dipole potential plays a permissive role in the clustering of ErbB receptors and that the effects of lipid rafts on ligand binding and receptor signaling can be partially attributed to the dipole potential.

Original languageEnglish
Article number35850
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Oct 24 2016

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Epidermal Growth Factor
Cluster Analysis
Ligands
Energy Transfer
Protein-Tyrosine Kinases
Intercellular Signaling Peptides and Proteins
Proteins
Phosphotransferases
Lipids
Peptides
Mutation
ErbB Receptors

ASJC Scopus subject areas

  • General

Cite this

The Dipole Potential Modifies the Clustering and Ligand Binding Affinity of ErbB Proteins and Their Signaling Efficiency. / Kovács, T.; Batta, G.; Hajdu, Tímea; Szabó, Ágnes; Váradi, Tímea; Zákány, Florina; Csomós, István; Szöllősi, J.; Nagy, Peter.

In: Scientific Reports, Vol. 6, 35850, 24.10.2016.

Research output: Contribution to journalArticle

Kovács, T. ; Batta, G. ; Hajdu, Tímea ; Szabó, Ágnes ; Váradi, Tímea ; Zákány, Florina ; Csomós, István ; Szöllősi, J. ; Nagy, Peter. / The Dipole Potential Modifies the Clustering and Ligand Binding Affinity of ErbB Proteins and Their Signaling Efficiency. In: Scientific Reports. 2016 ; Vol. 6.
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