2023/12/19 by Krishna C. Mudumbi, Eric Burns, David J. Schodt +11 · 1 voice · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Monoclonal and Polyclonal Antibodies Research #RNA and protein synthesis mechanisms #Toxin Mechanisms and Immunotoxins
paper · doi:10.1016/j.celrep.2023.113603
openalex publication_date 2023/12/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase with important roles in many cellular processes as well as in cancer and other diseases. EGF binding promotes EGFR dimerization and autophosphorylation through interactions that are well understood structurally. How these dimers relate to higher-order EGFR oligomers seen in cell membranes, however, remains unclear. Here, we used single-particle tracking (SPT) and Förster resonance energy transfer imaging to examine how each domain of EGFR contributes to receptor oligomerization and the rate of receptor diffusion in the cell membrane. Although the extracellular region of EGFR is sufficient to drive receptor dimerization, we find that the EGF-induced EGFR slowdown seen by SPT requires higher-order oligomerization-mediated in part by the intracellular tyrosine kinase domain when it adopts an active conformation. Our data thus provide important insight into the interactions required for higher-order EGFR assemblies involved in EGF signaling.