HGF-induced serine 897 phosphorylation of EphA2 regulates epithelial morphogenesis of MDCK cells in 3D culture
HGF-induced serine 897 phosphorylation of EphA2 regulates epithelial morphogenesis of MDCK cells in 3D culture
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DOI：
10.1242/jcs.163790
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发表时间：
2015-05-15
影响因子：
4
通讯作者：
Katoh, Hironori
中科院分区：
文献类型：
--
作者：
Harada, Kohei;Negishi, Manabu;Katoh, Hironori
EphA2在来源于上皮细胞的多种癌症中表达上调，并与癌细胞的迁移和侵袭能力有关。在此，我们研究了EphA2在三维培养的Madin-Darby犬肾(MDCK)细胞上皮形态发生中的作用。我们发现，EphA2通过肝细胞生长因子(HGF)刺激，通过磷脂酰肌醇3-激酶(PI3K)-Akt依赖的机制在丝氨酸残基897上被磷酸化，并且这种磷酸化是MDCK包囊中延伸形成所必需的，这是小管发生的第一步。相比之下，使用配体ewitinA1的刺激使丝氨酸残基897上的EphA2去磷酸化，并抑制HGF诱导的形态变化。此外，小GTP酶RhoG的激活参与了HGF诱导的EphA2下游延伸的形成。这些观察表明，EphA2的不依赖配体的活性有助于上皮的形态发生。
Expression of EphA2 is upregulated in various cancers that are derived from epithelial cells and correlates with the ability of a cancer cell to undergo migration and invasion. Here we have investigated the role of EphA2 in the epithelial morphogenesis of Madin-Darby canine kidney (MDCK) cells in three-dimensional culture. We show that EphA2 is phosphorylated on serine residue 897 through hepatocyte growth factor (HGF) stimulation using a phosphatidylinositol 3-kinase (PI3K)-Akt-dependent mechanism and that this phosphorylation is required for the formation of extensions, the first step of tubulogenesis, in MDCK cysts. By contrast, stimulation using the ligand ephrinA1 dephosphorylates EphA2 on serine residue 897 and suppresses the HGF-induced morphological change. Furthermore, activation of the small GTPase RhoG is involved in the HGF-induced formation of extensions downstream of EphA2. These observations suggest that a ligand-independent activity of EphA2 contributes to epithelial morphogenesis.