Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and migration
Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and migration
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DOI：
10.1074/jbc.m500010200
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发表时间：
2005-08-12
影响因子：
4.8
通讯作者：
Nakamoto, M
中科院分区：
文献类型：
--
作者：
Matsuoka, H;Obama, H;Nakamoto, M
EphB6是Eph受体酪氨酸激酶家族中一个独特的成员，它的激酶结构域包含几个保守氨基酸的改变，并且催化活性不高。虽然EphB6在多种胚胎和成人组织中都有表达，但这种受体的生物学功能在很大程度上是未知的。在本研究中，我们检测了EphB6在细胞粘附和迁移中的功能。我们证明EphB6对不同浓度的ephrin-B2配体产生双相效应；EphB6在低浓度ephrin-B2刺激下促进细胞粘附和迁移，而在高浓度ephrin-B2刺激下诱导排斥和抑制迁移。缺少细胞质结构域的截断的EphB6受体对细胞粘附和迁移表现出单相阳性作用，表明细胞质结构域对其负作用至关重要。EphB6与Src家族激酶Fyn相关。高浓度ephrin-B2通过Src家族激酶活性诱导EphB6酪氨酸磷酸化。这些结果表明，EphB6可以正向和负向调节细胞粘附和迁移，并提示Src家族激酶对该受体酪氨酸磷酸化是功能转变的分子开关。
EphB6 is a unique member in the Eph family of receptor tyrosine kinases in that its kinase domain contains several alterations in conserved amino acids and is catalytically inactive. Although EphB6 is expressed both in a variety of embryonic and adult tissues, biological functions of this receptor are largely unknown. In the present study, we examined the function of EphB6 in cell adhesion and migration. We demonstrated that EphB6 exerted biphasic effects in response to different concentrations of the ephrin-B2 ligand; EphB6 promoted cell adhesion and migration when stimulated with low concentrations of ephrin-B2, whereas it induced repulsion and inhibited migration upon stimulation with high concentrations of ephrin-B2. A truncated EphB6 receptor lacking the cytoplasmic domain showed monophasic-positive effects on cell adhesion and migration, indicating that the cytoplasmic domain is essential for the negative effects. EphB6 is constitutively associated with the Src family kinase Fyn. High concentrations of ephrin-B2 induced tyrosine phosphorylation of EphB6 through an Src family kinase activity. These results indicate that EphB6 can both positively and negatively regulate cell adhesion and migration, and suggest that tyrosine phosphorylation of the receptor by an Src family kinase acts as the molecular switch for the functional transition.