title: EphA receptors form a complex with caspase-8 to induce apoptotic cell death.
abstract: EphA7 has been implicated in the regulation of apoptotic cell death in neural epithelial cells. In this report, we provide evidence that EphA7 interacts with caspase-8 to induce apoptotic cell signaling. First, a pull-down assay using biotinylated ephrinA5-Fc showed that EphA7 coprecipitated with wild type caspase-8 or catalytically inactive caspase-8 mutant. Second, co-transfection of EphA7 with caspase-8 significantly increased the number of cleaved caspase-3 positive apoptotic cells under an experimental condition where transfection of EphA7 or caspase-8 alone did not affect cell viability or apoptosis. EphA4 also had a causative role in inducing apoptotic cell death with caspase-8, whereas EphA8 did not. Third, caspase-8 catalytic activity was essential for the apoptotic signaling cascade, whereas tyrosine kinase activity of the EphA4 receptor was not. Interestingly, we found that kinaseinactive EphA4 was well co-localized at the plasma membrane with catalytically inactive caspase-8, suggesting that an interaction between these mutant proteins was more stable. Finally, we observed that the extracellular region of the EphA7 receptor was critical for interacting with caspase-8, whereas the cytoplasmic region of EphA7 was not. Therefore, we propose that Eph receptors physically associate with a transmembrane protein to form an apoptotic signaling complex and that this unidentified receptorlike protein acts as a biochemical linker between the Eph receptor and caspase-8.
authors: Department of Biological Science.
authors: Haeryung
authors: H
authors: Lee
authors: Department of Biological Science.
authors: Sunjung
authors: S
authors: Park
authors: College of Pharmacy and Research Institute of Pharmaceutical Science, Sookmyung Women's University, Seoul 140-742, Korea.
authors: Young-Sook
authors: YS
authors: Kang
authors: Department of Biological Science.
authors: Soochul
authors: S
authors: Park
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D010766:Phosphorylation; D036141:Receptor, EphA7 / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D036141:Receptor, EphA7; C505530:CASP8 protein, human; D053181:Caspase 8