EphA2 receptor unliganded dimers suppress EphA2 pro-tumorigenic signaling

Deo R. Singh, Fozia Ahmed, Christopher King, Nisha Gupta, Matt Salotto, Elena B. Pasquale, Kalina Hristova

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


The EphA2 receptor tyrosine kinase promotes cell migration and cancer malignancy through a ligand-and kinase-independent distinctive mechanism that has been linked to high Ser-897 phosphorylation and low tyrosine phosphorylation. Here, we demonstrate that EphA2 forms dimers in the plasma membrane of HEK293T cells in the absence of ephrin ligand binding, suggesting that the current seeding mechanism model of EphA2 activation is incomplete. We also characterize a dimerizationdeficient EphA2 mutant that shows enhanced ability to promote cell migration, concomitant with increased Ser-897 phosphorylation and decreased tyrosine phosphorylation compared with EphA2 wild type. Our data reveal a correlation between unliganded dimerization and tumorigenic signaling and suggest that EphA2 pro-tumorigenic activity is mediated by the EphA2 monomer. Thus, a therapeutic strategy that aims at the stabilization of EphA2 dimers may be beneficial for the treatment of cancers linked to EphA2 overexpression.

Original languageEnglish (US)
Pages (from-to)27271-27279
Number of pages9
JournalJournal of Biological Chemistry
Issue number45
StatePublished - Nov 6 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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