Biased activation of the receptor tyrosine kinase HER2

  • HER2 belongs to the ErbB sub-family of receptor tyrosine kinases and regulates cellular proliferation and growth. Different from other ErbB receptors, HER2 has no known ligand. Activation occurs through heterodimerization with other ErbB receptors and their cognate ligands. This suggests several possible activation paths of HER2 with ligand-specific, differential response, which so far remained unexplored. Using single-molecule tracking and the diffusion profile of HER2 as a proxy for activity, we measured the activation strength and temporal profile in live cells. We found that HER2 is strongly activated by EGFR-targeting ligands EGF and TGFα, yet with a distinguishable temporal fingerprint. The HER4-targeting ligands EREG and NRGβ1 showed weaker activation of HER2, a preference for EREG, and a delayed response to NRGβ1. Our results indicate a selective ligand response of HER2 that may serve as a regulatory element. Our experimental approach is easily transferable to other membrane receptors targeted by multiple ligands.

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Author:Claudia Catapano, Johanna V. RahmORCiD, Marjan OmerORCiD, Laura TeodoriORCiD, Jørgen KjemsORCiDGND, Marina DietzORCiDGND, Mike HeilemannORCiDGND
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2023/04/20
Date of first Publication:2023/04/20
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/08/01
Edition:Version 2
Page Number:24
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International