JAKs go nuclear: emerging role of nuclear JAK1 and JAK2 in gene expression and cell growth.
JAKs go nuclear: emerging role of nuclear JAK1 and JAK2 in gene expression and cell growth.
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DOI：
10.3109/08977194.2011.614949
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Booz GW
中科院分区：
文献类型：
--
作者：
Zouein FA;Duhé RJ;Booz GW
四种 JAKS 组成一个细胞内非受体酪氨酸激酶家族，它们首先作为 I 型和 II 型细胞因子受体的信号传导介质而受到关注。随后，发现 JAK 参与胰岛素受体、许多受体酪氨酸激酶和某些 G 蛋白偶联受体的下游信号传导。尽管已鉴定出 JAK 的许多细胞质靶标，但发现它们的主要作用是 STAT 转录因子的磷酸化和激活。通过 STAT，JAK 激活与细胞应激、增殖和分化相关的基因表达。 JAK 在造血、炎症和免疫中尤其重要，异常的 JAK 活性与许多疾病有关，包括类风湿性关节炎、牛皮癣、真性红细胞增多症和骨髓增殖性疾病。尽管曾经被认为严格存在于细胞质中，但最近的证据表明，JAK1 和 JAK2 存在于某些细胞的细胞核中，通常处于与细胞高生长速率相关的条件下。现在已证明核 JAK 可以通过激活除 STAT 之外的其他转录因子并发挥表观遗传作用（例如通过磷酸化组蛋白 H3）来影响基因表达。后一种作用会抑制整体基因表达，并与白血病发生有关。核 JAK 可能在干细胞生物学中也发挥作用。在这里，我们描述了理解 JAK1 和 JAK2 的非规范核作用的最新进展。
The four JAKS comprise a family of intracellular, non-receptor tyrosine kinases that first gained attention as signaling mediators of the type I and type II cytokine receptors. Subsequently, the JAKs were found to be involved in signaling downstream of the insulin receptor, a number of receptor tyrosine kinases, and certain G-protein coupled receptors. Although a number of cytoplasmic targets for the JAKs have been identified, their predominant action was found to be the phosphorylation and activation of the STAT transcription factors. Through the STATs, the JAKs activate gene expression linked to cellular stress, proliferation, and differentiation. The JAKs are especially important in haematopoiesis, inflammation, and immunity, and aberrant JAK activity has been implicated in a number of disorders including rheumatoid arthritis, psoriasis, polycythemia vera, and myeloproliferative diseases. Although once thought to reside strictly in the cytoplasm, recent evidence shows that JAK1 and JAK2 are present in the nucleus of certain cells often under conditions associated with high rates of cell growth. Nuclear JAKs have now been shown to affect gene expression by activating other transcription factors besides the STATs and exerting epigenetic actions, for example, by phosphorylating histone H3. The latter action derepresses global gene expression and has been implicated in leukemogenesis. Nuclear JAKs may have a role as well in stem cell biology. Here we describe recent developments in understanding the noncanonical nuclear actions of JAK1 and JAK2.
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影响因子：
4.8
作者：
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