The EphA2 receptor is activated through induction of distinct, ligand-dependent oligomeric structures

Deo R. Singh, Pranjali Kanvinde, Christopher King, Elena B. Pasquale, Kalina Hristova

Research output: Contribution to journalArticlepeer-review

Abstract

The EphA2 receptor tyrosine kinase is capable of activating multiple diverse signaling pathways with roles in processes such as tissue homeostasis and cancer. EphA2 is known to form activated oligomers in the presence of ephrin-A ligands. Here, we characterize the lateral interactions between full-length EphA2 molecules in the plasma membrane in the presence of three types of ligands (dimeric ephrinA1-Fc, monomeric ephrinA1, and an engineered peptide ligand) as well as in the absence of ligand, using a quantitative FRET technique. The data show that EphA2 forms higher-order oligomers and two different types of dimers that all lead to increased EphA2 tyrosine phosphorylation, which is indicative of increased kinase-dependent signaling. We find that different ligands stabilize conformationally distinct oligomers that are assembled through two different interfaces. Our results suggest that these different oligomeric assemblies could have distinct signaling properties, contributing to the diverse activities of the EphA2 receptor.

Original languageEnglish (US)
Article number15
JournalCommunications biology
Volume1
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

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