Carboni L, Tacconi S, Carletti R, Bettini E, Ferraguti F
Department of Pharmacology, Glaxo Wellcome S.p.A., Medicines Research Centre, Verona, Italy.
Neuroscience. 1997 Sep;80(1):147-60. doi: 10.1016/s0306-4522(97)00005-5.
Stress-activated protein kinase/extracellular signal-regulated protein kinase-1/c-Jun NH2-terminal kinase kinase is a dual-specificity kinase which phosphorylates and activates stress-activated protein kinase/c-Jun NH2-terminal kinase, a recently discovered mitogen-activated protein kinase that is stimulated by stressful stimuli and that regulates cellular transcriptional activity. The distribution of the messenger RNA encoding for stress-activated protein kinase/extracellular signal-regulated protein kinase-1 was evaluated in the adult and developing rat central nervous system. In situ hybridization with a 35S-labelled 45mer oligodeoxynucleotide probe was used to map the distribution of the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA in postnatal day 1, 3, 6, 9, 12, 15, 18, 21 and adult rat brains. Specific labelling was generally associated with neuronal profiles. In the adult central nervous system, high hybridization signals were observed in the hippocampus, the granular layer of the cerebellum, the medial habenula, the anterodorsal thalamic nucleus, the red nucleus, the pontine nuclei, the facial nucleus, the motor and mesencephalic nuclei of the trigeminal nerve, the hypoglossal nucleus, the vestibular nucleus and the nucleus ambiguus. Intermediate levels were present in diencephalic and mesencephalic regions and in the neocortex, while basal ganglia displayed a low hybridization signal. In the developing brain, the heterogeneous distribution of the hybridization signal observed in the adult brain was already present, but in the hippocampus and basal ganglia the stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels were significantly higher at postnatal day 3 and during the second postnatal week than in the adult. The results show that stress-activated protein kinase/extracellular signal-regulated protein kinase-1 is widely expressed in the rat central nervous system and co-localizes with its substrate stress-activated protein kinase. The observed changes in stress-activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels during postnatal development suggest a role for this protein in the maturation of brain circuits.
应激激活蛋白激酶/细胞外信号调节蛋白激酶-1/c-Jun氨基末端激酶激酶是一种双特异性激酶，它磷酸化并激活应激激活蛋白激酶/c-Jun氨基末端激酶，后者是最近发现的一种丝裂原激活蛋白激酶，受应激刺激激活并调节细胞转录活性。对成年和发育中的大鼠中枢神经系统中编码应激激活蛋白激酶/细胞外信号调节蛋白激酶-1的信使核糖核酸分布进行了评估。使用与35S标记的45聚体寡脱氧核苷酸探针进行原位杂交，以定位出生后第1、3、6、9、12、15、18、21天以及成年大鼠脑中应激激活蛋白激酶/细胞外信号调节蛋白激酶-1信使核糖核酸的分布。特异性标记通常与神经元形态相关。在成年中枢神经系统中，在海马体、小脑颗粒层、内侧缰核、丘脑前背核、红核、脑桥核、面神经核、三叉神经运动核和中脑核、舌下神经核、前庭核和疑核中观察到高杂交信号。间脑和中脑区域以及新皮层中存在中等水平，而基底神经节显示低杂交信号。在发育中的大脑中，已观察到成年大脑中杂交信号的异质性分布，但在海马体和基底神经节中，出生后第3天和出生后第二周的应激激活蛋白激酶/细胞外信号调节蛋白激酶-1信使核糖核酸水平明显高于成年期。结果表明，应激激活蛋白激酶/细胞外信号调节蛋白激酶-1在大鼠中枢神经系统中广泛表达，并与其底物应激激活蛋白激酶共定位。在出生后发育过程中观察到的应激激活蛋白激酶/细胞外信号调节蛋白激酶-1信使核糖核酸水平的变化表明该蛋白在脑回路成熟中起作用。
