Role of MAP kinase in neurons

Abstract

Extracellular stimuli such as neurotransmitters, neurotrophins, and growth factors in the brain regulate critical cellular events, including synaptic transmission, neuronal plasticity, morphological differentiation and survival. Although many such stimuli trigger Ser/Thr-kinase and tyrosine-kinase cascades, the extracellular signal-regulated kinases, ERK1 and ERK2, prototypic members of the mitogen-activated protein (MAP) kinase family, are most attractive candidates among protein kinases that mediate morphological differentiation and promote survival in neurons. ERK1 and ERK2 are abundant in the central nervous system (CNS) and are activated during various physiological and pathological events such as brain ischemia and epilepsy. In cultured hippocampal neurons, simulation of glutamate receptors can activate ERK signaling, for which elevation of intracellular Ca2+ is required. In addition, brain-derived neurotrophic factor and growth factors also induce the ERK signaling and here, receptor-coupled tyrosine kinase activation has an association. We describe herein intracellular cascades of ERK signaling through neurotransmitters and neurotrophic factors. Putative functional implications of ERK and other MAP-kinase family members in the central nervous system are give attention.

Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-κB in hippocampal neuronal cell culture

“…Our results suggest that CXCL10 could be neuroprotective under some neuroinflammatory conditions. Moreover, because ERK1/2, CREB and NF-κB are important regulators of neuronal physiology (Fukunaga and Miyamoto, 1998), our studies raise the possibility that CXCL10 actions on these signal transduction molecules could lead to a significant alteration in neuronal physiology during neuroinflammatory conditions. (C).…”

“…Recent studies show that in cultured mouse CNS neurons acutely applied CXCL10 (25 nM) can result in activation of the ERK1/2 pathway (Xia et al, 2000), a pathway that plays a central role in CNS synaptic functions and cell growth and survival (Bahr et al, 2002;Bailey et al, 1997;Fukunaga and Miyamoto, 1998;Hetman and Gozdz, 2004;Kornhauser and Greenberg, 1997;Vaudry et al, 2002;Waetzig and Herdegen, 2003). Little is known about the signal transduction pathways activated in CNS cells by chronic exposure to CXCL10.…”

“…Our previous immunohistochemical studies ( Nelson and Gruol, 2004) showed that the cultured hippocampal neurons are strongly immunoreactive for CXCR3, the receptor for CXCL10, whereas astrocytes are only weakly immunoreactive, consistent with higher level of CXCR3 in neurons than in glia and the effects of CXCL10 on signal transduction molecules occurring primarily in the neuronal population. ERK1/2 activation plays a key role in promoting neuronal growth, differentiation, survival, as well as in long-term memory (Bailey et al, 1997;Fukunaga and Miyamoto, 1998;Hetman and Gozdz, 2004;Kornhauser and Greenberg, 1997). However, sustained ERK1/2 activation has been associated with neuronal death (Alessandrini et al, 1999;Murray et al, 1998;Runden et al, 1998).…”

“…Our current studies showing that chronic exposure to CXCL10 alters the levels of cell specific proteins in the hippocampal cultures also provides evidence for a CXCL10 signaling pathway in the hippocampal cells. Although limited information is available on the signaling pathway activated by CXCL10 in CNS neurons and glia, it has been reported that acute exposure to CXCL10 can activate the ERK1/2 pathway in neurons (Bonacchi et al, 2001;Xia et al, 2000), a pathway that mediates a number of neuronal functions including synaptic plasticity, neuronal growth, differentiation, and survival (Bahr et al, 2002;Bailey et al, 1997;Fukunaga and Miyamoto, 1998;Hetman and Gozdz, 2004;Kornhauser and Greenberg, 1997;Vaudry et al, 2002;Waetzig and Herdegen, 2003). In the hippocampal cultures, acute exposure to CXCL10 increased the level of activated (i.e., phosphorylated) ERK1/2 (no effect on total ERK1/2), consistent with an involvement of the ERK1/2 pathway in the actions of acute CXCL10 on the hippocampal cells (Nelson and Bajova, 2007) However, It is unknown if the ERK1/2 pathway is involved in actions of CXCL10 in the hippocampal cultures under conditions of chronic CXCL10 exposure.…”

“…Binding of CXCL10 to CXCR3 can activate a variety of intracellular signal transduction pathways (Bonacchi et al, 2001;Moser and Loetscher, 2001;Xia et al, 2000), including the Ras/ERK signaling pathway, a pathway that is known to play an important role in functions such as growth, differentiation, survival, and long-term memory (Bahr et al, 2002;Bailey et al, 1997;Fukunaga and Miyamoto, 1998;Hetman and Gozdz, 2004;Kornhauser and Greenberg, 1997;Vaudry et al, 2002;Waetzig and Herdegen, 2003). However, prolonged activation of ERK has been reported to participate in neuronal death induced by various stimuli (Alessandrini et al, 1999;Murray et al, 1998;Runden et al, 1998).…”