Ephexin4-mediated promotion of cell migration and anoikis resistance is regulated by serine 897 phosphorylation of EphA2.
Ephexin4-mediated promotion of cell migration and anoikis resistance is regulated by serine 897 phosphorylation of EphA2.
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DOI：
10.1016/j.fob.2013.01.002
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发表时间：
2013
期刊：
影响因子：
2.6
通讯作者：
Katoh H
中科院分区：
文献类型：
--
作者：
Kawai H;Kobayashi M;Hiramoto-Yamaki N;Harada K;Negishi M;Katoh H
EphA2是由Akt通过丝氨酸897(S897)上的磷酸化来激活的，以促进癌细胞的运动和侵袭，而不依赖于它的配体ePhin的刺激。在这里，我们证明了EphA2的S897磷酸化增强了EphA2和Ephexin4之间的相互作用，Ephexin4是小GTP酶RhoG的鸟嘌呤核苷酸交换因子。EphA2基因S897A突变取消了EphA2/Ephexin4介导的RhoG激活、促进细胞迁移和对失巢凋亡的抵抗。我们的结果表明，S897磷酸化的EphA2招募Ephexin4来促进细胞迁移和抗失巢凋亡，提供了S897磷酸化EphA2与肿瘤进展之间的分子联系。▸S897对EphA2的磷酸化增强了EphA2和Ephexin4之间的相互作用。▸S897A突变抑制EphA2介导的RhoG激活。▸S897A突变可阻断EphA2/Ephexin4介导的细胞迁移和抗失巢凋亡。
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. ▸ S897 phosphorylation of EphA2 strengthens the interaction between EphA2 and Ephexin4. ▸ S897A mutation of EphA2 suppresses EphA2-mediated RhoG activation. ▸ S897A mutation blocks EphA2/Ephexin4-mediated cell migration and anoikis resistance.
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影响因子：
78.5
作者：
Pasquale, Elena B.
通讯作者：
Pasquale, Elena B.
影响因子：
3.5
作者：
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作者：
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通讯作者：
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影响因子：
3.3
作者：
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通讯作者：
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