Filamin A forms a complex with EphA2 and regulates EphA2 serine 897 phosphorylation and glioblastoma cell proliferation

Abstract

EphA2 is phosphorylated on serine 897 (S897) in response to growth factors such as epidermal growth factor (EGF) and on tyrosine 588 (Y588) in response to its ligand ephrinA1, causing different cellular responses. In this study, we show that the actin-binding protein Filamin A forms a complex with EphA2 and promotes its S897 phosphorylation and glioblastoma cell proliferation. Suppression of Filamin A expression by siRNAs inhibited glioblastoma cell proliferation induced by EGF stimulation or overexpression of EphA2. Knockdown of Filamin A inhibited EGF-induced S897 phosphorylation of EphA2, whereas it had little effect on ephrinA1-induced Y588 phosphorylation of EphA2. Furthermore, Filamin A expression affected the subcellular localization of EphA2. This study suggests that Filamin A selectively promotes EphA2 S897 phosphorylation and plays an important role in glioblastoma cell proliferation.