Flood D G, Finn J P, Walton K M, Dionne C A, Contreras P C, Miller M S, Bhat R V
Department of Molecular Biology, Cephalon, Inc., West Chester, Pennsylvania 19380, USA.
J Comp Neurol. 1998 Aug 31;398(3):373-92. doi: 10.1002/(sici)1096-9861(19980831)398:3<373::aid-cne6>3.0.co;2-x.
Cell survival, death, and stress signals are transduced from the cell surface to the cytoplasm and nucleus via a cascade of phosphorylation events involving the mitogen-activated protein kinase (MAPK) family. We compared the distribution of p42 mitogen-activated protein kinase (p42MAPK) and its activator MAPK or ERK kinase (MEK1; involved in transduction of growth and differentiation signals), with c-Jun N-terminal kinase (JNK1) and its activator MEK4 (involved in transduction of stress and death signals) in the adult rat central nervous system. All four kinases were present in the cytoplasm, dendrites, and axons of neurons. The presence of p42MAPK and JNK1 in dendrites and axons, as well as in cell bodies, suggests a role for these kinases in phosphorylation and regulation of cytoplasmic targets. A high degree of correspondence was found between the regional distribution of MEK1 and p42MAPK. Immunostaining for MEK1 and p42MAPK was intense in olfactory structures, neocortex, hippocampus, striatum, midline, and interlaminar thalamic nuclei, hypothalamus, brainstem, Purkinje cells, and spinal cord. In addition to neurons, p42MAPK was also present in oligodendrocytes. Whereas MEK4 was ubiquitously distributed, JNK1 was more selective. Immunostaining for MEK4 and JNK1 was intense in the olfactory bulb, lower cortical layers, the cholinergic basal forebrain, most nuclei of the thalamus, medial habenula, and cranial motor nuclei. The distribution of MEK1 and p42MAPK proteins only partially overlapped with that of MEK4 and JNK1. This suggests that the growth/differentiation and death/stress pathways affected by these kinases may not necessarily act to counterbalance each other in response to extracellular stimuli. The differential distribution of these kinases may control the specificity of neuronal function to extracellular signals.
细胞存活、死亡及应激信号通过涉及丝裂原活化蛋白激酶（MAPK）家族的一系列磷酸化事件从细胞表面转导至细胞质和细胞核。我们比较了成年大鼠中枢神经系统中p42丝裂原活化蛋白激酶（p42MAPK）及其激活剂MAPK或细胞外信号调节激酶（MEK1；参与生长和分化信号的转导）与c-Jun氨基末端激酶（JNK1）及其激活剂MEK4（参与应激和死亡信号的转导）的分布情况。所有这四种激酶均存在于神经元的细胞质、树突和轴突中。p42MAPK和JNK1在树突、轴突以及细胞体中的存在表明这些激酶在细胞质靶点的磷酸化和调节中发挥作用。发现MEK1和p42MAPK的区域分布之间存在高度对应性。MEK1和p42MAPK的免疫染色在嗅觉结构、新皮质、海马体、纹状体、中线和层间丘脑核、下丘脑、脑干、浦肯野细胞和脊髓中强烈。除神经元外，p42MAPK也存在于少突胶质细胞中。虽然MEK4分布广泛，但JNK1更具选择性。MEK4和JNK1的免疫染色在嗅球、皮质下层、胆碱能基底前脑、丘脑的大多数核、内侧缰核和颅运动核中强烈。MEK1和p42MAPK蛋白的分布仅部分与MEK4和JNK1的分布重叠。这表明受这些激酶影响的生长/分化和死亡/应激途径在响应细胞外刺激时不一定相互抵消。这些激酶的差异分布可能控制神经元功能对细胞外信号的特异性。
