Ligands with different dimeric configurations potently activate the EphA2 receptor and reveal its potential for biased signaling.

ABSTRACT: The EphA2 receptor tyrosine kinase activates signaling pathways with different, and sometimes opposite, effects in cancer and other pathologies. Thus, highly specific and potent biased ligands that differentially control EphA2 signaling responses could be therapeutically valuable. Here, we use EphA2-specific monomeric peptides to engineer dimeric ligands with three different geometric configurations to combine a potential ability to differentially modulate EphA2 signaling responses with the high potency and prolonged receptor residence time characteristic of dimeric ligands. The different dimeric peptides readily induce EphA2 clustering, autophosphorylation and signaling, the best with sub-nanomolar potency. Yet, there are differences in two EphA2 signaling responses induced by peptides wi

SUBMITTER: Gomez-Soler M 

PROVIDER: S-EPMC8858996 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature