Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors

Peter W Janes, Bettina Griesshaber, Lakmali SK Atapattu Mudiyanselage, Eva Nievergall, Linda LP Hii, Anneloes Mensinga, Chanly Chheang, Bryan W Day, Andrew W Boyd, Phillippe I Bastiaens, Claus Jorgensen, Tony Pawson, Martin Lackmann

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61 Citations (Scopus)

Abstract

Eph receptors interact with ephrin ligands on adjacent cells to facilitate tissue patterning during normal and oncogenic development, in which unscheduled expression and somatic mutations contribute to tumor progression. EphA and B subtypes preferentially bind A- and B-type ephrins, respectively, resulting in receptor complexes that propagate via homotypic Eph-Eph interactions. We now show that EphA and B receptors cocluster, such that specific ligation of one receptor promotes recruitment and cross-activation of the other. Remarkably, coexpression of a kinase-inactive mutant EphA3 with wild-type EphB2 can cause either cross-activation or cross-inhibition, depending on relative expression. Our findings indicate that cellular responses to ephrin contact are determined by the EphA/EphB receptor profile on a given cell rather than the individual Eph subclass. Importantly, they imply that in tumor cells coexpressing different Ephs, functional mutations in one subtype may cause phenotypes that are a result of altered signaling from heterotypic rather from homotypic Eph clusters.
Original languageEnglish
Pages (from-to)1033 - 1045
Number of pages13
JournalJournal of Cell Biology
Volume195
Issue number6
DOIs
Publication statusPublished - 2011

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