Identification of tubulin as a substrate of Jak2 tyrosine kinase and its role in Jak2-dependent signaling
Identification of tubulin as a substrate of Jak2 tyrosine kinase and its role in Jak2-dependent signaling
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DOI：
10.1021/bi700101n
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发表时间：
2007-06-19
期刊：
影响因子：
2.9
通讯作者：
Sayeski, Peter P.
中科院分区：
文献类型：
--
作者：
Ma, Xianyue;Sayeski, Peter P.
Jak 2是一种非受体酪氨酸激酶，在许多细胞信号转导系统中起作用。在真核细胞中表达了大量的重组Jak 2蛋白，并纯化了一个未知的55 kDa蛋白，经质谱和Western blot分析鉴定，该55 kDa蛋白为微管蛋白的α-和β-亚型。生物化学实验确定Jak 2和微管蛋白特异性地相互结合，并且Jak 2结合微管蛋白的区域是假激酶结构域。免疫荧光表明，Jak 2和微管蛋白（微管）共定位在完整的细胞内。Jak 2和微管蛋白之间的共缔合的功能结果是Jak 2磷酸化微管蛋白的酪氨酸残基。具体而言，响应于生长激素，微管蛋白以Jak 2依赖的方式磷酸化。微管蛋白也被发现与信号转导和转录激活因子1（STAT 1）相互作用，并参与STAT 1的核转运。因此，这项工作表明微管蛋白是Jak 2的底物，并促进Jak 2/STAT 1依赖性信号传导。
Jak2 is a nonreceptor tyrosine kinase that acts in numerous cellular signal transduction systems. Here, large amounts of recombinant Jak2 protein were expressed in eukaryotic cells, and an unknown 55 kDa protein was copurified with it. Mass spectrometry and Western blot analysis identified the 55 kDa protein as the alpha- and beta-isoforms of tubulin. Biochemical experiments determined that Jak2 and tubulin specifically coassociate with one another, and the region of Jak2 that binds tubulin is the pseudokinase domain. Immunofluoresence indicated that Jak2 and tubulin (microtubules) colocalize within intact cells. The functional consequence of the coassociation between Jak2 and tubulin is that Jak2 phosphorylates tubulin on tyrosine residues. Specifically, in response to growth hormone, tubulin was phosphorylated in a Jak2-dependent manner. Tubulin was also found to interact with signal transducers and activators of transcription 1 (STAT1) and be involved in STAT1 nuclear transport. As such, this work suggests that tubulin is a substrate of Jak2 and facilitates Jak2/STAT1-dependent signaling.