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首页> 外文期刊>Cellular Signalling >Dvl3 translocates IPMK to the cell membrane in response to Wnt
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Dvl3 translocates IPMK to the cell membrane in response to Wnt

机译：Dvl3响应Wnt将IPMK易位到细胞膜

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摘要

Wnt3a binds Frizzled-1 and the LRP5/6 co-receptors, ultimately activating Lef/Tcf-sensitive gene transcription in development. Inositol polyphosphate multikinase, IPMK, which possesses inositol phosphate kinase and lipid inositol kinase activities, is essential in Wnt3a regulation of its canonical pathway as well as physiologically in AMPK signaling. In the current report we show that translocation of IPMK to the cell membrane, where its substrates exist in high abundance, is obligate to its function in Wnt signaling. Translocation of IPMK to the cell membrane occurs within 5. min after Wnt3a stimulation. IPMK ducking onto Dishevelled-3(Dvl3)requires a PDZ domain and the COOH-terminal prolyly-rich tail of Dvl3. Wnt3a-stimulates mobilization of Dvl3 to the cell membrane, translocating IPMK to the cell membrane also, to facilitate downstream signaling of Frizzled1. Deletion mutant of IPMK lacking the NH2-terminal variable region, IPMKδN, fails to translocate to the cell membrane and to propagate canonical signaling. Targeting the IPMKδN back to the cell membrane by addition of an isoprenylated CAAX box rescues its function in Wnt3a downstream signaling.
机译：Wnt3a结合Frizzled-1和LRP5 / 6共同受体，最终激活发育中的Lef / Tcf敏感基因转录。具有肌醇磷酸激酶和脂质肌醇激酶活性的肌醇多磷酸多激酶IPMK在Wnt3a调节其经典途径以及在AMPK信号传导中起着至关重要的作用。在当前的报告中，我们表明IPMK到细胞膜的转运（其底物高度丰富）在其Wnt信号传导中起着重要作用。 Wnt3a刺激后5分钟内，IPMK易位至细胞膜。躲在Dishevelled-3（Dvl3）上的IPMK需要一个PDZ域和Dvl3的COOH末端富含脯氨酸的尾巴。 Wnt3a刺激Dvl3动员到细胞膜，也将IPMK转移到细胞膜，以促进Frizzled1的下游信号传导。缺少NH2末端可变区的IPMK缺失突变体IPMKδN无法转运至细胞膜并传播规范信号。通过添加异戊二烯化的CAAX盒将IPMKδN靶向回到细胞膜，可在Wnt3a下游信号传导中恢复其功能。

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