Nemo-like kinase is involved in NGF-induced neurite outgrowth via phosphorylating MAP1B and paxillin
Nemo-like kinase is involved in NGF-induced neurite outgrowth via phosphorylating MAP1B and paxillin
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DOI：
10.1111/j.1471-4159.2009.06400.x
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发表时间：
2009-12-01
影响因子：
4.7
通讯作者：
Itoh, Motoyuki
中科院分区：
文献类型：
--
作者：
Ishitani, Tohru;Ishitani, Shizuka;Itoh, Motoyuki
神经生长因子（NGF）通过调节细胞骨架结构和细胞粘附促进神经突起的生长。这些活动受到蛋白质磷酸化的调节。Nemo-like kinase（NLK）是一种进化上保守的MAP激酶样激酶，其磷酸化几种转录因子。虽然已知NLK在神经系统中以相对高的水平表达，但其功能尚不清楚。我们发现，NGF促进NLK易位到PC 12细胞的前缘，并触发其中的NLK激酶活性。活化的NLK直接磷酸化微管相关蛋白-1B（MAP 1B）和粘着斑衔接蛋白（paxillin）。NLK的敲低减弱桩蛋白和MAP 1B的磷酸化，并抑制NGF诱导的F-肌动蛋白和神经突生长的重新分布。我们还发现NLK是一种LiCl敏感的激酶。已知LiCl阻断PC 12细胞中NGF诱导的神经突生长以及MAP 1B和桩蛋白的磷酸化。因此，LiCl的作用部分是通过阻断NLK活性介导的。这些结果表明，NLK控制NGF信号下游的细胞骨架的动力学。
Nerve growth factor (NGF) promotes neurite outgrowth through regulating cytoskeletal organization and cell adhesion. These activities are modulated by protein phosphorylation. Nemo-like kinase (NLK) is an evolutionarily conserved MAP kinase-like kinase that phosphorylates several transcription factors. Although NLK is known to be expressed at relatively high levels in the nervous system, its function is not well understood. We found that NGF promotes the translocation of NLK to PC12 cells' leading edges, and triggers NLK kinase activity in them. Activated NLK directly phosphorylates microtubule-associated protein-1B (MAP1B) and the focal adhesion adaptor protein, paxillin. Knockdown of NLK attenuates the phosphorylation of both paxillin and MAP1B and inhibits both the NGF-induced re-distribution of F-actin and neurite outgrowth. We also discovered that NLK is a LiCl-sensitive kinase. LiCl is known to block NGF-induced neurite outgrowth and the phosphorylation of MAP1B and paxillin in PC12 cells. Therefore, the effects of LiCl are mediated in part by blocking NLK activity. These results suggest that NLK controls the dynamics of the cytoskeleton downstream of NGF signaling.