Eph receptors are negatively controlled by protein tyrosine phosphatase receptor type O
Eph receptors are negatively controlled by protein tyrosine phosphatase receptor type O
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DOI：
10.1038/nn1697
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发表时间：
2006-06-01
影响因子：
25
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
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作者：
Shintani, Takafumi;Ihara, Masaru;Noda, Masaharu
Eph受体通过与其配体肝配蛋白结合后酪氨酸残基的自磷酸化而被激活;然而，负责Eph受体负调节的蛋白质酪氨酸磷酸酶（PTPs）尚未阐明。在这里，我们确定了蛋白酪氨酸磷酸酶受体O型（Ptpro）作为一个特定的PTP，有效地去磷酸化EphA和EphB受体作为底物。生化分析表明，Ptpro去磷酸化的磷酸酪氨酸残基保守的质膜区域，这是必需的激活和信号传递的Eph受体。因此，Ptpro似乎调节Eph受体的最大活化量。使用小鸡retinotectal投影系统，我们表明，Ptpro控制的敏感性视网膜轴突ephrins，从而有一个至关重要的作用，在建立地形投影。我们的研究结果解释了决定体内Eph受体对肝配蛋白反应阈值的分子机制。
Eph receptors are activated by the autophosphorylation of tyrosine residues upon the binding of their ligands, the ephrins; however, the protein tyrosine phosphatases (PTPs) responsible for the negative regulation of Eph receptors have not been elucidated. Here, we identified protein tyrosine phosphatase receptor type O (Ptpro) as a specific PTP that efficiently dephosphorylates both EphA and EphB receptors as substrates. Biochemical analyses revealed that Ptpro dephosphorylates a phosphotyrosine residue conserved in the juxtamembrane region, which is required for the activation and signal transmission of Eph receptors. Ptpro thus seems to moderate the amount of maximal activation of Eph receptors. Using the chick retinotectal projection system, we show that Ptpro controls the sensitivity of retinal axons to ephrins and thereby has a crucial role in the establishment of topographic projections. Our findings explain the molecular mechanism that determines the threshold of the response of Eph receptors to ephrins in vivo.