The regional distribution of extracellularly regulated kinase-1 and -2 messenger RNA in the adult rat central nervous system

Abstract

It has previously been shown that an intracellular serine/threonine kinase known as extracellularly 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 variety of cells including neurons. Extracellularly regulated kinases phosphorylate transcription factors, cytoskeletal proteins and enzyme targets. As such they are believed to function in neuronal signal transduction. In situ hybridization histochemistry using synthetic oligonucleotide probes has been used to identify cells in the adult rat central nervous system containing messenger RNAs coding for two isoforms of extracellularly regulated kinase. Extracellularly regulated kinase-2 messenger RNA was observed in many regions including the cerebral cortex, olfactory bulb, hippocampus, amygdala, basal ganglia (except the globus pallidus and endopeduncular nucleus), basal nucleus, thalamus, hypothalamus, brain stem nuclei, cerebellum and neurons in the spinal cord. Extracellularly regulated kinase-1 messenger RNA was confined to fewer regions than extracellularly regulated kinase-2 messenger RNA. Hybridization 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 particular 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 region, whereas extracellularly regulated kinase-2 was present in all neurons of the hippocampus. There were no CNS regions that expressed extracellularly regulated kinase-1 but not extracellularly regulated kinase-2; however, neurons of the dorsal root ganglia showed extracellularly regulated kinase-1 but not extracellularly regulated kinase-2 messenger RNA. Although extracellularly regulated kinase-1 and extracellularly regulated kinase-2 expression was selectively neuronal in the brain, extracellularly regulated kinase-1 messenger RNA was localized to glia in the spinal cord. The distinct cellular distribution of individual extracellularly regulated kinases in the adult rat CNS suggests that they play unique signalling roles.