The p21-activated kinase, Shk1, is required for proper regulation of microtubule dynamics in the fission yeast, Schizosaccharomyces pombe
The p21-activated kinase, Shk1, is required for proper regulation of microtubule dynamics in the fission yeast, Schizosaccharomyces pombe
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DOI：
10.1046/j.1365-2958.2002.02882.x
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发表时间：
2002-04-01
影响因子：
3.6
通讯作者：
Marcus, S
中科院分区：
文献类型：
--
作者：
Qyang, YB;Yang, PR;Marcus, S
p21活化的激酶，Shk1，在分裂酵母中是正确建立细胞极性所必需的。我们最近发现，缺少必要的Shk1抑制剂Skb15，会导致分裂酵母的纺锤体缺陷，从而暗示Shk1是微管动力学的潜在调节剂。在这里，我们发现缺乏Shk1功能的细胞具有畸形的间期微管和有丝分裂微管纺锤体，对微管不稳定药物噻苯达唑（TBZ）过敏，对生长冷敏感。TBZ处理导致Shk1激酶活性下调，在细胞从药物中释放后迅速增加，从而提供了Shk1激酶功能与活性微管聚合之间的相关性。与Shk1作为微管动力学调节剂的作用一致，绿色荧光蛋白(GFP)-Shk1融合蛋白定位于间期微管和有丝分裂微管纺锤体，以及分裂酵母细胞的细胞末端和隔膜形成区。我们发现，细胞末端和微管定位蛋白Tea1的缺失加剧了Shk1部分缺失导致的生长和微管缺陷，而Shk1定位于由Tea1突变细胞产生的非法生长尖端。Tea1是一种细胞末端和微管定位蛋白，以前在裂变酵母中被认为是微管动力学的调节剂。我们的研究结果表明，Shk1是裂变酵母微管动力学的适当调节所必需的，并暗示Tea1是潜在的Shk1调节因子。
The p21-activated kinase, Shk1, is required for the proper establishment of cell polarity in the fission yeast, Schizosaccharomyces pombe . We showed recently that loss of the essential Shk1 inhibitor, Skb15, causes significant spindle defects in fission yeast, thus implicating Shk1 as a potential regulator of microtubule dynamics. Here, we show that cells deficient in Shk1 function have malformed interphase microtubules and mitotic microtubule spindles, are hypersensitive to the microtubule-destabilizing drug thiabendazole (TBZ) and cold sensitive for growth. TBZ treatment causes a downregulation of Shk1 kinase activity, which increases rapidly after release of cells from the drug, thus providing a correlation between Shk1 kinase function and active microtubule polymerization. Consistent with a role for Shk1 as a regulator of microtubule dynamics, green fluorescent protein (GFP)-Shk1 fusion proteins localize to interphase microtubules and mitotic microtubule spindles, as well as to cell ends and septum-forming regions of fission yeast cells. We show that loss of Tea1, a cell end- and microtubule-localized protein previously implicated as a regulator of microtubule dynamics in fission yeast, exacerbates the growth and microtubule defects resulting from partial loss of Shk1 and that Shk1 localizes to illicit growth tips produced by tea1 mutant cells. Our results demonstrate that Shk1 is required for the proper regulation of microtubule dynamics in fission yeast and implicate Tea1 as a potential Shk1 regulator.