Carletti R, Tacconi S, Bettini E, Ferraguti F
Department of Pharmacology, Glaxo Research Laboratories, Verona, Italy.
Neuroscience. 1995 Dec;69(4):1103-10. doi: 10.1016/0306-4522(95)00284-p.
Mitogen-activated protein kinases are important mediators of signal transduction from the cell surface to the nucleus and their activation has been implicated in a wide array of physiological processes. The extracellular-signal-regulated kinases are the archetypal and best studied members of the mitogen activated protein kinases. Recently, additional subgroups of mitogen activated protein kinases have been identified which exhibit distinct regulatory elements, substrate specificity and respond to diverse extracellular stimuli. Among these newly identified protein kinases are the rat stress-activated protein kinases. Despite a rapidly expanding literature on the biochemical properties of stress-activated protein kinases no anatomical data are yet available. In the present study, we have investigated the regional distribution of messenger RNA transcripts for stress-activated protein kinases in the adult rat central nervous system and compared this distribution to that observed for extracellular-signal-regulated kinases. Intense labelling for stress-activated protein kinases could be detected in discrete brain areas with high levels in hippocampus, neocortex and some nuclei of the brain stem. The apparent hybridization signal appeared to be selectively neuronal. Stress-activated protein kinases and extracellular-signal-regulated kinases hybridization patterns appeared generally dissimilar although a certain degree of co-expression in some brain areas, such as the hippocampal formation, could be observed. These results reveal an extreme complexity in the mitogen-activated protein kinase signalling pathway and suggest the existence of parallel mitogen-activated protein kinase cascades that can be activated independently or in some cases simultaneously, by extracellular stimuli.
丝裂原活化蛋白激酶是细胞表面到细胞核信号转导的重要介质，其激活与多种生理过程有关。细胞外信号调节激酶是丝裂原活化蛋白激酶中典型且研究最多的成员。最近，已鉴定出丝裂原活化蛋白激酶的其他亚组，它们表现出不同的调节元件、底物特异性，并对多种细胞外刺激作出反应。这些新鉴定的蛋白激酶中包括大鼠应激激活蛋白激酶。尽管关于应激激活蛋白激酶生化特性的文献迅速增加，但尚无解剖学数据。在本研究中，我们研究了成年大鼠中枢神经系统中应激激活蛋白激酶信使核糖核酸转录本的区域分布，并将其与细胞外信号调节激酶的分布进行了比较。在离散的脑区可检测到应激激活蛋白激酶的强烈标记，海马、新皮层和脑干的一些核团中水平较高。明显的杂交信号似乎具有选择性神经元特征。应激激活蛋白激酶和细胞外信号调节激酶的杂交模式总体上不同，尽管在某些脑区，如海马结构，可观察到一定程度的共表达。这些结果揭示了丝裂原活化蛋白激酶信号通路的极端复杂性，并表明存在平行的丝裂原活化蛋白激酶级联反应，它们可被细胞外刺激独立激活或在某些情况下同时激活。
