title: Ephexin4-mediated promotion of cell migration and anoikis resistance is regulated by serine 897 phosphorylation of EphA2.
abstract: EphA2 is activated through phosphorylation on serine 897 (S897) by Akt to promote cancer cell motility and invasion, independently of stimulation by ephrin, its ligand. Here we show that S897 phosphorylation of EphA2 strengthens the interaction between EphA2 and Ephexin4, a guanine nucleotide exchange factor for the small GTPase RhoG. S897A mutation of EphA2 abolished the EphA2/Ephexin4-mediated RhoG activation, promotion of cell migration, and resistance to anoikis. Our results suggest that S897-phosphorylated EphA2 recruits Ephexin4 to promote cell migration and anoikis resistance, providing a molecular link between S897 phosphorylation of EphA2 and tumor progression.
authors.affiliation: Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawai
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Nao
authors.initials: N
authors.lastname: Hiramoto-Yamaki
authors.forename: Kohei
authors.initials: K
authors.lastname: Harada
authors.forename: Manabu
authors.initials: M
authors.lastname: Negishi
authors.forename: Hironori
authors.initials: H
authors.lastname: Katoh
keywords: Anoikis resistance; Cell migration; EphA2; Ephexin; GAP, GTPase-activating protein; GEF, guanine nucleotide exchange factor; RhoG; RhoGEF; SAM, sterile-α-motif; poly-HEMA, poly-hydroxyethylmethacrylate.