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神內(nèi)清

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Two genes on chromosome 21, namely dual specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) and regulator of calcineurin 1 (RCAN1), have been implicated in some of the phenotypic characteristics of Down syndrome, including the early onset of Alzheimer disease. Although a link between Dyrk1A and RCAN1 and the nuclear factor of activated T cells (NFAT) pathway has been reported, it remains unclear whether Dyrk1A directly interacts with RCAN1. In the present study, Dyrk1A is shown to directly interact with and phosphorylate RCAN1 at Ser(112) and Thr(192) residues。Dyrk1A-mediated phosphorylation of RCAN1 at Ser(112) primes the protein for the GSK3beta-mediated phosphorylation of Ser(108). Phosphorylation of RCAN1 at Thr(192) by Dyrk1A enhances the ability of RCAN1 to inhibit the phosphatase activity of calcineurin (Caln), leading to reduced NFAT transcriptional activity and enhanced Tau phosphorylation. These effects are mediated by the enhanced binding of RCAN1 to Caln and its extended half-life caused by Dyrk1A-mediated phosphorylation. Furthermore, an increased expression of phospho-Thr(192)-RCAN1 was observed in the brains of transgenic mice overexpressing the Dyrk1A protein. These results suggest a direct link between Dyrk1A and RCAN1 in the Caln-NFAT signaling and Tau hyperphosphorylation pathways, supporting the notion that the synergistic interaction between the chromosome 21 genes RCAN1 and Dyrk1A is associated with a variety of pathological features associated with DS。只翻譯紅色內(nèi)容

[ Last edited by 神內(nèi)清 on 2013-1-20 at 19:29 ]

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神內(nèi)清: 金幣+25, ★★★很有幫助, 不錯(cuò)，挺專(zhuān)業(yè)的，個(gè)別小地方的錯(cuò)誤！可見(jiàn)英語(yǔ)水平確實(shí)很高！ 2013-01-21 16:00:57

雙特異性酪氨酸磷酸化調(diào)節(jié)激酶1A(Dyrk1A)介導(dǎo)鈣調(diào)磷酸酶調(diào)節(jié)蛋白1(RCAN1)Ser112位點(diǎn)的磷酸化引發(fā)了糖原合酶激酶-3β(GSK3beta)介導(dǎo)的蛋白Ser108位點(diǎn)的磷酸化。RCAN1上的Thr192位點(diǎn)經(jīng)RCAN1磷酸化后，可增強(qiáng)RCAN1抑制鈣調(diào)磷酸酶的磷酸酶活性，導(dǎo)致T細(xì)胞活化核因子(NFAT)轉(zhuǎn)錄活性的降低和Tau磷酸化的增強(qiáng)。此外，在過(guò)量表達(dá)Dyrk1A的轉(zhuǎn)基因小鼠的腦中觀測(cè)到磷酸化-Thr192-RCAN1表達(dá)量的增加。這些結(jié)果暗示了在Caln-NFAT信號(hào)通路和Tau高度磷酸化通路中Dyrk1A 和 RCAN1有直接的聯(lián)系，支持了21號(hào)染色體上Dyrk1A 和 RCAN1基因間具有協(xié)同作用的觀點(diǎn)，而該作用與唐氏綜合癥(DS)相關(guān)的許多病理特征是有關(guān)的。

[ Last edited by zhtear99 on 2013-1-21 at 10:17 ]

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