IMMUNOLOCALIZATION OF THE MITOGEN-ACTIVATED PROTEIN-KINASES P42(MAPK)AND JNK1, AND THEIR REGULATORY KINASES MEK1 AND MEK4, IN ADULT-RAT CENTRAL-NERVOUS-SYSTEM

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. W e compared the distribution of p42 mitogen-activated protein kinase (p 42(MAPK)) and its activator MAPK or ERK kinase (MEK1; involved in tran sduction of growth and differentiation signals), with c-Jun N-terminal kinase (JNK1) and its activator MEK4 (involved in transduction of str ess and death signals) in the adult rat central nervous system. All fo ur kinases were present in the cytoplasm, dendrites, and axons of neur ons. The presence of p42(MAPK) and JNK1 in dendrites and axons, as wel l as in cell bodies, suggests a role for these kinases in phosphorylat ion and regulation of cytoplasmic targets. A high degree of correspond ence was found between the regional distribution of MEK1 and p42(MAPK) . Immunostaining for MEK1 and p42(MAPK) was intense in olfactory struc tures, neocortex, hippocampus, striatum, midline, and interlaminar tha lamic nuclei, hypothalamus, brainstem, Purkinje cells, and spinal cord . In addition to neurons, p43(MAPK) was also present in oligodendrocyt es. 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 distribu tion of MEK1 and p42(MAPK) proteins only partially overlapped with tha t of MEK4 and JNK1. This suggests that the growth/differentiation and death/stress pathways affected by these kinases may not necessarily ac t to counterbalance each other in response to extracellular stimuli. T he differential distribution of these kinases may control the specific ity of neuronal function to extracellular signals. J. Comp. Neurol. 39 8:373-392, 1998. (C) 1998 Wiley-Liss, Inc.