Hirai Syu-ichi, Kawaguchi Atumi, Suenaga Jun, Ono Makiko, Cui De Feng, Ohno Shigeo
Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, 3-9, Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Gene Expr Patterns. 2005 Apr;5(4):517-23. doi: 10.1016/j.modgep.2004.12.002.
C-Jun N-terminal kinase (JNK) is implicated in regulating the various cellular events during neural development that include differentiation, apoptosis and migration. MUK/DLK/ZPK is a MAP kinase kinase kinase (MAPKKK) enzyme that activates JNK via MAP kinase kinases (MAPKK) such as MKK7. We show here that the expression of MUK/DLK/ZPK protein in the developing mouse embryo is almost totally specific for the neural tissues, including central, peripheral, and autonomic nervous systems. The only obvious exception is the liver, in which the protein is temporally expressed at around E11. The expression becomes obvious in the neurons of the brain and neural crest tissues at embryonic day 10 (E10) after neuron production is initiated. By E14, MUK/DLK/ZPK proteins are found in various neural tissues including the brain, spinal cord, sensory ganglia (such as trigeminal and dorsal root ganglia), and the sympathetic and visceral nerves. The localization of MUK/DLK/ZPK protein in neural cells almost consistently overlapped that of betaIII-tubulin, a neuron specific tubulin isoform, and both proteins were more concentrated in axons than in cell bodies and dendrites. The intensely overlapping localization of betaIII-tubulin and MUK/DLK/ZPK indicated that this protein kinase is tightly associated with the microtubules of neurons.
C-Jun氨基末端激酶（JNK）参与调节神经发育过程中的各种细胞活动，包括分化、凋亡和迁移。MUK/DLK/ZPK是一种丝裂原活化蛋白激酶激酶激酶（MAPKKK）酶，它通过诸如MKK7等丝裂原活化蛋白激酶激酶（MAPKK）激活JNK。我们在此表明，MUK/DLK/ZPK蛋白在发育中的小鼠胚胎中的表达几乎完全特异性地存在于神经组织中，包括中枢、外周和自主神经系统。唯一明显的例外是肝脏，该蛋白在胚胎第11天左右在肝脏中短暂表达。在神经元产生开始后的胚胎第10天（E10），该蛋白在大脑和神经嵴组织的神经元中表达变得明显。到E14时，在包括大脑、脊髓、感觉神经节（如三叉神经节和背根神经节）以及交感神经和内脏神经在内的各种神经组织中都发现了MUK/DLK/ZPK蛋白。MUK/DLK/ZPK蛋白在神经细胞中的定位几乎始终与βIII-微管蛋白（一种神经元特异性微管蛋白异构体）的定位重叠，并且这两种蛋白在轴突中比在细胞体和树突中更集中。βIII-微管蛋白和MUK/DLK/ZPK的强烈重叠定位表明这种蛋白激酶与神经元的微管紧密相关。
