Immunolocalization of the mitogen-activated protein kinases p42MAPK and JNK1, and their regulatory kinases MEK1 and MEK4, in adult rat central nervous system

Abstract

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. We compared the distribution of p42 mitogen-activated protein kinase (p42MAPK) and its activator MAPK or ERK kinase (MEK1; involved in transduction of growth and differentiation signals), with c-Jun N-terminal kinase (JNK1) and its activator MEK4 (involved in transduction of stress and death signals) in the adult rat central nervous system. All four kinases were present in the cytoplasm, dendrites, and axons of neurons. The presence of p42MAPK and JNK1 in dendrites and axons, as well as in cell bodies, suggests a role for these kinases in phosphorylation and regulation of cytoplasmic targets. A high degree of correspondence was found between the regional distribution of MEK1 and p42MAPK. Immunostaining for MEK1 and p42MAPK was intense in olfactory structures, neocortex, hippocampus, striatum, midline, and interlaminar thalamic nuclei, hypothalamus, brainstem, Purkinje cells, and spinal cord. In addition to neurons, p42MAPK was also present in oligodendrocytes. 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 distribution of MEK1 and p42MAPK proteins only partially overlapped with that of MEK4 and JNK1. This suggests that the growth/differentiation and death/stress pathways affected by these kinases may not necessarily act to counterbalance each other in response to extracellular stimuli. The differential distribution of these kinases may control the specificity of neuronal function to extracellular signals.

Odorant-Induced Activation of Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase in the Olfactory Bulb Promotes Survival of Newly Formed Granule Cells

“…However, pErkϩ cells were absent from the glomerular layer. This distribution of pErk is in good agreement with a previous report showing that Erk protein is abundant in granule cells and less in mitral cells and the glomerular layer (Flood et al, 1998).…”

“…Immunohistochemical studies have also revealed that the MAPK is expressed in granule cells (Flood et al, 1998), suggesting the possibility that MAPK may contribute to the survival of granule cells and/or activity-dependent plasticity. However, there are several important unanswered questions.…”

Regulation of Extracellular Signal-Regulated Kinase by Cannabinoids in Hippocampus

“…ERKs are present in brain and are particularly abundant in the hippocampus (Fiore et al, 1993;Flood et al, 1998). Anandamide (1 M), 2-AG (1 M), synthetic CB1-R agonists (1 M CP 55940 and 100 M WIN 55212-2), and THC increased the active form of ERK1 and ERK2 in hippocampal slices ( Fig.…”

Catecholaminergic Control of Mitogen-Activated Protein Kinase Signaling in Paraventricular Neuroendocrine NeuronsIn VivoandIn Vitro: A Proposed Role during Glycemic Challenges

“…Peyssonnaux and Eychène, 2001). Because MEK1 isoforms have been localized to PVH (Flood et al, 1998), we hypothesized that NE-induced recruitment of ERK1/2 may be mediated by activation of MEK. To test this, we pretreated hypothalamic slices with U0126, a highly selective MEK inhibitor (Duncia et al, 1998), and tested the ability of NE to trigger phospho-ERK1/2 under these conditions.…”