THE REGIONAL DISTRIBUTION OF EXTRACELLULARLY REGULATED KINASE-1 AND KINASE-2 MESSENGER-RNA IN THE ADULT-RAT CENTRAL-NERVOUS-SYSTEM

It has previously been shown that an intracellular serine/threonine ki nase known as extra-cellularly signal-regulated kinase, also known as microtubule-associated protein kinase, is phosphorylated and activated in response to a range of hormones, growth factors (e.g. nerve growth factor) and neurotransmitters (e.g. N-methyl-D-aspartate) in a variet y of cells including neurons. Extracellularly regulated kinases phosph orylate transcription factors, cytoskeletal proteins and enzyme target s. As such they are believed to function in neuronal signal transducti on. In situ hybridization histochemistry using synthetic oligonucleoti de probes has been used to identify cells in the adult rat central ner vous system containing messenger RNAs coding for two isoforms of extra cellularly regulated kinase. Extracellularly regulated kinase-2 messen ger RNA was observed in many regions including the cerebral cortex, ol factory bulb, hippocampus, amygdala, basal ganglia (except the globus pallidus and endopeduncular nucleus), basal nucleus, thalamus, hypotha lamus. brain stem nuclei, cerebellum and neurons in the spinal cord. E xtracellularly regulated kinase-1 messenger RNA was confined to fewer regions than extracellularly regulated kinase-2 messenger RNA. Hybridi zation signals for extracellularly regulated kinase-1 were seen in the olfactory bulb, cortex, regions of the hippocampus, amygdala, nucleus basalis of Maynert, substantia nigra, some hypothalamic and brainstem nuclei and cerebellum, as well as neurons of the spinal cord. Of part icular interest, extracellularly regulated kinase-1 messenger RNA was absent from all regions of the basal ganglia and thalamus. Furthermore , extracellularly regulated kinase-1 was almost absent from the CA1 re gion, whereas extracellularly regulated kinase-2 was present in all ne urons of the hippocampus. There were no CNS regions that expressed ext racellularly regulated kinase-1 but not extracellularly regulated kina se-2; however, neurons of the dorsal root ganglia showed extracellular ly regulated kinase-1 but not extracellularly regulated kinase-2 messe nger RNA. Although extracellularly regulated kinase-1 and extracellula rly regulated kinase-2 expression was selectively neuronal in the brai n. extracellularly regulated kinase-1 messenger RNA was localized to g lia in the spinal cord. The distinct cellular distribution of individu al extracellularly regulated kinases in the adult rat CNS suggests tha t they play unique signalling roles.