Phosphorylation-dependent control of ZIPK nuclear import is species specific.
Phosphorylation-dependent control of ZIPK nuclear import is species specific.
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ZIPK 核输入的磷酸化依赖性控制具有物种特异性。
DOI：
10.1016/j.cellsig.2010.09.016
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发表时间：
2011
影响因子：
4.8
通讯作者：
Haystead,TimothyAJ
中科院分区：
文献类型：
--
作者：
Weitzel,DouglasH;Chambers,Jenica;Haystead,TimothyAJ
ZIPK（拉链相互作用蛋白激酶）是一种不依赖 Ca2+ 的蛋白激酶，可促进平滑肌和非肌肉细胞中的肌球蛋白磷酸化。最近的一份报告试图澄清关于 ZIPK 在非肌肉细胞中的亚细胞定位的争论（Shoval et. al. (2007) Plos Genetics. 3: 1884–1883）。鼠类（小鼠和大鼠）ZIPK 中关键磷酸化位点 (T299) 的物种特异性缺失似乎将其引导至细胞核，而人 ZIPK 中 T299 位点的存在与细胞质定位相关。 T299 紧邻假定的核定位序列 (NLS)，磷酸化时可能会掩盖其功能，因此解释了细胞内定位的物种特异性二分法。然而，尽管小鼠 ZIPK (mZIPK) 缺乏对控制人类 ZIPK (hZIPK) 亚细胞定位至关重要的 T299 残基，但突变分析表明该 NLS 控制位点在小鼠环境中不起作用。组成型活性 Rho 促进人类 ZIPK 突变体在细胞质中的保留，否则该突变体将定位于细胞核。内源性 hZIPK 对核输出抑制剂瘦霉素 B 表现出敏感性，表明细胞质和细胞核之间的持续穿梭依赖于 T299 去磷酸化。因此，人和鼠 ZIPK 的 C 端结构域表现出相当不同的核输入和输出功能。我们的结论是，就 ZIPK 而言，鉴于细胞内定位和运动的巨大差异，物种之间的研究可能无法直接进行比较。
ZIPK (zipper-interacting protein kinase) is a Ca2+-independent protein kinase that promotes myosin phosphorylation in both smooth muscle and non-muscle cells. A recent report attempted to clarify a debate over the subcellular localization of ZIPK in non-muscle cells (Shoval et. al. (2007) Plos Genetics. 3: 1884–1883). A species-specific loss of a key phosphorylation site (T299) in murine (mouse and rat) ZIPK seems to direct it to the nucleus, while the presence of the T299 site in human ZIPK correlates with cytoplasmic localization. T299 is immediately adjacent to a putative nuclear localization sequence (NLS) and may mask its function when phosphorylated, therefore explaining the species-specific dichotomy of intracellular localization. However, despite the murine ZIPK (mZIPK) lacking the T299 residue that is critical for controlling human ZIPK (hZIPK) subcellular localization, mutational analysis showed that this NLS control locus is nonfunctional in the murine context. A constitutively active Rho promoted the cytoplasmic retention of a human ZIPK mutant that would otherwise localize to the nucleus. Endogenous hZIPK showed sensitivity to the nuclear export inhibitor leptomycin B, suggesting a continuous shuttling between cytoplasm and nucleus that is dependent upon T299 dephosphorylation. Thus, the C-terminal domain of human and murine ZIPK demonstrated quite divergent nuclear import and export functionality. We conclude that in the case of ZIPK, studies between the species may not be directly comparable to each other given the gross differences in intracellular localization and movement.
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