Characterization of the zebrafish homolog of zipper interacting protein kinase.
Characterization of the zebrafish homolog of zipper interacting protein kinase.
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DOI：
10.3390/ijms150711597
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发表时间：
2014-06-30
影响因子：
5.6
通讯作者：
Weiser DC
中科院分区：
文献类型：
--
作者：
Carr BW;Basepayne TL;Chen L;Jayashankar V;Weiser DC
拉链相互作用蛋白激酶（ZIPK）是一种保守的脊椎动物特异性平滑肌和非肌肉细胞中肌动球蛋白收缩性调节因子。与其他ZIPK直系同源物相比，小鼠ZIPK在序列和调控方面经历了不寻常的分歧。在人类中，亚细胞定位由苏氨酸299和300的磷酸化控制。相反，ZIPK在小鼠和大鼠中的亚细胞定位是通过与PAR-4的相互作用来控制的。我们对ZIPK的斑马鱼直系同源物的调节进行了比较生物化学表征。与人类直系同源物一样，斑马鱼ZIPK经历核质穿梭，并且在细胞质中丰富，不像主要是核大鼠ZIPK。大鼠ZIPK，而不是人或斑马鱼ZIPK，与斑马鱼PAR-4相互作用。激活哺乳动物直系同源物所需的保守残基的突变废除了斑马鱼ZIPK的活性。与人类直系同源物相比，斑马鱼ZIPK中苏氨酸299和300的突变对活性或亚细胞定位没有影响。因此，我们发现斑马鱼ZIPK的功能与人ZIPK的功能非常相似，与鼠直系同源物非常不同，但亚细胞定位的调节并不保守。
Zipper-interacting protein kinase (ZIPK) is a conserved vertebrate-specific regulator of actomyosin contractility in smooth muscle and non-muscle cells. Murine ZIPK has undergone an unusual divergence in sequence and regulation compared to other ZIPK orthologs. In humans, subcellular localization is controlled by phosphorylation of threonines 299 and 300. In contrast, ZIPK subcellular localization in mouse and rat is controlled by interaction with PAR-4. We carried out a comparative biochemical characterization of the regulation of the zebrafish ortholog of ZIPK. Like the human orthologs zebrafish ZIPK undergoes nucleocytoplasmic-shuttling and is abundant in the cytoplasm, unlike the primarily nuclear rat ZIPK. Rat ZIPK, but not human or zebrafish ZIPK, interacts with zebrafish PAR-4. Mutation of the conserved residues required for activation of the mammalian orthologs abrogated activity of the zebrafish ZIPK. In contrast to the human ortholog, mutation of threonine 299 and 300 in the zebrafish ZIPK has no effect on the activity or subcellular localization. Thus, we found that zebrafish ZIPK functions in a manner most similar to the human ZIPK and quite distinct from murine orthologs, yet the regulation of subcellular localization is not conserved.
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