Janus kinase (Jak) subcellular localization revisited -: The exclusive membrane localization of endogenous Janus kinase 1 by cytokine receptor interaction uncovers the Jak•receptor complex to be equivalent to a receptor tyrosine kinase
Janus kinase (Jak) subcellular localization revisited -: The exclusive membrane localization of endogenous Janus kinase 1 by cytokine receptor interaction uncovers the Jak•receptor complex to be equivalent to a receptor tyrosine kinase
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DOI：
10.1074/jbc.m404202200
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发表时间：
2004-08-20
影响因子：
4.8
通讯作者：
Haan, C
中科院分区：
文献类型：
--
作者：
Behrmann, I;Smyczek, T;Haan, C
Janus激酶被认为是与细胞因子受体的细胞质区域组成性结合的细胞质激酶，并且Janus激酶（Jaks）对于细胞因子信号转导是至关重要的。我们研究了Jak 1定位使用亚细胞分级分离技术和荧光显微镜（免疫荧光和黄色荧光蛋白标记的Jaks）。在不同的实验方法中，我们发现Jak 1（以及Jak 2和Tyk 2）主要位于膜上。与以前的报道相反，我们没有观察到Jak蛋白在细胞核内或细胞质中的显着量。细胞质定位观察到的Jak 1突变体L 80 A/Y81 A，这是无法与细胞因子受体，表明Jak 1没有一个强大的内在膜结合潜力，只有受体结合是至关重要的膜招聘。最后，我们表明，Jak 1仍然是一个膜定位蛋白细胞因子刺激后。这些数据有力地支持了细胞因子受体Janus激酶复合物可被视为受体酪氨酸激酶的假设。
The Janus kinases are considered to be cytoplasmic kinases that constitutively associate with the cytoplasmic region of cytokine receptors, and the Janus kinases (Jaks) are crucial for cytokine signal transduction. We investigated Jak1 localization using subcellular fractionation techniques and fluorescence microscopy (immunofluorescence and yellow fluorescent protein-tagged Jaks). In the different experimental approaches we found Jak1 (as well as Jak2 and Tyk2) predominantly located at membranes. In contrast to previous reports we did not observe Jak proteins in significant amounts within the nucleus or in the cytoplasm. The cytoplasmic localization observed for the Jak1 mutant L80A/Y81A, which is unable to associate with cytokine receptors, indicates that Jak1 does not have a strong intrinsic membrane binding potential and that only receptor binding is crucial for the membrane recruitment. Finally we show that Jak1 remains a membrane-localized protein after cytokine stimulation. These data strongly support the hypothesis that cytokine receptor Janus kinase complexes can be regarded as receptor tyrosine kinases.