Open AccessEphexin4‐mediated promotion of cell migration and anoikis resistance is regulated by serine 897 phosphorylation of EphA2
Author(s) -
Kawai Hiromu,
Kobayashi Masakazu,
Hiramoto-Yamaki Nao,
Harada Kohei,
Negishi Manabu,
Katoh Hironori
Publication year - 2013
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2013.01.002
Subject(s) - anoikis , serine , phosphorylation , promotion (chess) , microbiology and biotechnology , eph receptor a2 , chemistry , cancer research , biology , biochemistry , programmed cell death , apoptosis , political science , receptor tyrosine kinase , politics , law
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.