title: Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Janes
authors.forename: Bettina
authors.initials: B
authors.lastname: Griesshaber
authors.forename: Lakmali
authors.initials: L
authors.lastname: Atapattu
authors.forename: Eva
authors.initials: E
authors.lastname: Nievergall
authors.forename: Linda L
authors.initials: LL
authors.lastname: Hii
authors.forename: Anneloes
authors.initials: A
authors.lastname: Mensinga
authors.forename: Chanly
authors.initials: C
authors.lastname: Chheang
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Day
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Boyd
authors.forename: Philippe I
authors.initials: PI
authors.lastname: Bastiaens
authors.forename: Claus
authors.initials: C
authors.lastname: Jørgensen
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: Martin
authors.initials: M
authors.lastname: Lackmann
mesh_terms: D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005910:Glioma / Q000201:enzymology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D058105:Polymerization; D011471:Prostatic Neoplasms / Q000201:enzymology; D036081:Receptors, Eph Family / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D036081:Receptors, Eph Family