Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38

Harper, Sarah; LoGrasso, Philip V.

doi:10.1016/s0898-6568(01)00148-6

Cited by 282 publications

(225 citation statements)

References 147 publications

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“…They regulate cell survival, cell death, proliferation and/or differentiation. [1][2][3] Generally, activation of the ERK forms of MAPK causes survival responses, whereas activation of the p38 and c-Jun NH2-terminal kinase (JNK) promotes cell death. In response to various stimuli, specific MAPK kinase kinases such as MLK1 and MKK7 are activated and sequentially phosphorylate the JNK kinase.…”

Section: Introductionmentioning

confidence: 99%

“…Once activated, JNK phosphorylates c-Jun, which in turn modulates the expression of many target genes. [1][2][3] The action specificity of JNK requires the presence of a scaffold protein termed c-Jun NH2-terminal kinase interacting protein-1 (JIP-1). 4 JIP-1 was initially cloned from a mouse library using JNK as a bait in a two-hybrid system.…”

Section: Introductionmentioning

confidence: 99%

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Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

et al. 2003

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Islet-brain1 (IB1) or c-Jun NH2 terminal kinase interacting protein-1 (JIP-1), the product of the MAPK8IP1 gene, functions as a neuronal scaffold protein to allow signalling specificity. IB1/ JIP-1 interacts with many cellular components including the reelin receptor ApoER2, the lowdensity lipoprotein receptor-related protein (LRP), kinesin and the Alzheimer's amyloid precursor protein. Coexpression of IB1/JIP-1 with other components of the c-Jun NH2 terminal-kinase (JNK) pathway activates the JNK activity; conversely, selective disruption of IB1/JIP-1 in mice reduces the stress-induced apoptosis of neuronal cells. We therefore hypothesized that IB1/JIP-1 is a risk factor for Alzheimer's disease (AD). By immunocytochemistry, we first colocalized the presence of IB1/JIP-1 with JNK and phosphorylated tau in neurofibrillary tangles. We next identified a À499A4G polymorphism in the 5' regulatory region of the MAPK8IP1 gene. In two separate French populations the À499A4G polymorphism of MAPK8IP1 was not associated with an increased risk to AD. However, when stratified on the þ 766C4T polymorphism of exon 3 of the LRP gene, the IB1/JIP-1 polymorphism was strongly associated with AD in subjects bearing the CC genotype in the LRP gene. The functional consequences of the -499A4G polymorphism of MAPK8IP1 was investigated in vitro. In neuronal cells, the G allele increased transcriptional activity and was associated with an enhanced binding activity. Taken together, these data indicate that the increased transcriptional activity in the presence of the G allele of MAPK8IP1 is a risk factor to the onset of in patients bearing the CC genotype of the LRP gene.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

et al. 2003

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“…13,14 MKK4 and MKK7 are the only known JNK activators. In some cell types, MKK4 activates JNK primarily by stress stimuli and MKK7 by inflammatory cytokines [15][16][17] but in neuronal excitotoxicity their contributions are still not known. 15 Both MKK4 8,9,18 and MKK7 8,9 have a JBD indicating that these activators of JNK are also targets and potentially sensitive to D-JNKI1.…”

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confidence: 99%

Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons

et al. 2006

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Excitotoxic insults induce c-Jun N-terminal kinase (JNK) activation, which leads to neuronal death and contributes to many neurological conditions such as cerebral ischemia and neurodegenerative disorders. The action of JNK can be inhibited by the Dretro-inverso form of JNK inhibitor peptide (D-JNKI1), which totally prevents death induced by N-methyl-D-aspartate (NMDA) in vitro and strongly protects against different in vivo paradigms of excitotoxicity. To obtain optimal neuroprotection, it is imperative to elucidate the prosurvival action of D-JNKI1 and the death pathways that it inhibits. In cortical neuronal cultures, we first investigate the pathways by which NMDA induces JNK activation and show a rapid and selective phosphorylation of mitogen-activated protein kinase kinase 7 (MKK7), whereas the only other known JNK activator, mitogen-activated protein kinase kinase 4 (MKK4) In many nervous system disorders, including cerebral ischemia, traumatic brain injury and neurodegenerative diseases, overactivation of N-methyl-d-aspartate (NMDA) receptors leads to neuronal damage, resulting in neuronal loss and consequent severe neurological impairment. This cascade of neuronal injury, referred to as 'excitotoxicity', is still only partly understood. Dying neurons activate complex signal transduction events to trigger their death program, and the c-Jun N-terminal kinase (JNK) pathway plays an important role in this process. 1 D-retro-inverso form of JNK inhibitor (D-JNKI1) is an extremely potent neuroprotectant against excitotoxicity of cortical neurons and against different in vivo paradigms of neurodegeneration. [2][3][4] The active part of this peptide contains a retro-inverso form of a 20-amino-acid sequence (JBD 20 ) from the JNK-binding domain (JBD) of the scaffold protein JNK-interacting protein-1 (IB1/JIP-1), and it blocks the access of JNK to many of its targets. [5][6][7] Recently, Negri et al. 8,9 performed a detailed re-examination of the JBD-containing proteins and identified 19 different substrates of JNK. They then proved in a cell-free assay that the JBD 20 sequence prevented interactions and phosphorylations by JNK of nine of these targets. Among these nine substrates, we have studied the following four that might participate in regulating the death of cortical neurons: (1) MADD/DENN (MAPK-activating death domain-containing protein/differentially expressed in normal and neoplastic cells); (2-3) mitogen-activated protein kinase kinase 4 (MKK4) and mitogen-activated protein kinase kinase 7 (MKK7), the two direct upstream activators of JNK and (4) the scaffold protein IB1/JIP-1.,In particularly, MADD/DENN was identified as a substrate for JNK3, 10 the isoform most clearly involved in excitotoxicity 11,12 and mostly expressed in the brain. [10][11][12] Increasing evidence supports a strong correlation between low MADD/ DENN expression and neuronal loss. 13,14 MKK4 and MKK7 are the only known JNK activators. In some cell types, MKK4 activates JNK primarily by stress stimuli and MKK7 by inflammatory cytoki...

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“…Compound mutant mice lacking the JNK1 and JNK2 genes suggested that JNK1 and JNK2 regulate region-specific apoptosis during early brain development (Kuan et al, 1999). Several lines of evidence have also suggested the pro-apoptotic roles of the p38 pathway (Xia et al, 1995;Kawasaki et al, 1997;Harper and LoGrasso et al, 2001), although they have not yet been supported by data of mice deficient for the p38 genes.Apoptosis signal-regulating kinase 1 (ASK1)/MAPKKK5 is a ubiquitously expressed MAPKKK that activates the JNK and p38 pathways by directly phosphorylating and thereby activating their respective MAPKKs, MKK4 (SEK1)/MKK7 and MKK3/MKK6 Ichijo et al, 1997) (Fig. 1).…”

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confidence: 99%

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confidence: 99%

Roles of MAPKKK ASK1 in Stress-Induced Cell Death.

Takeda

Matsuzawa

Nishitoh

et al. 2003

Cell Struct. Funct.

215

171

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ABSTRACT. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein (MAP) kinase kinase kinase that activates the c-Jun N-terminal kinase (JNK) and p38 MAP kinase signaling cascades. Recent findings from analyses of ASK1-deficient mice have revealed that ASK1 is required for apoptosis induced by oxidative stress, TNF and endoplasmic reticulum (ER) stress. In addition, several lines of evidence have suggested that ASK1 has diverse functions in the decision of cell fate beyond its pro-apoptotic activity. Thus, ASK1 appears to be a pivotal component not only in stress-induced cell death but also in a broad range of biological activities in order for cells to adapt to or oppose various stresses. Key words: MAPKKK/ASK1/JNK/p38/apoptosisThe mitogen-activated protein (MAP) kinase cascades are multifunctional signaling pathways that are evolutionally well conserved in all eukaryotic cells (Ichijo, 1999;Widmann, 1999;Kyriakis and Avruch, 2001). Three MAP kinase cascades that converge on ERKs, c-Jun N-terminal kinases (JNKs), and p38 MAP kinases have been extensively characterized, and each consists of three classes of serine/threonine kinases, MAP kinase, MAP kinase kinase (MAPKK, also referred to as MEK) and MAPKK kinase (MAPKKK). MAPKKK phosphorylates and thereby activates MAPKK, and activated MAPKK in turn phosphorylates and activates MAP kinase. Among the three MAP kinase cascades, two of them that converge on JNKs and p38 MAP kinases are preferentially activated by cytotoxic stresses such as UV radiation, X-ray, heat shock and osmotic shock, and by proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (Tibbles and Woodgett, 1999). One of the important biological responses mediated through these stress-activated MAP kinase pathways appears to be the decision of cell fate by regulating apoptosis. The possible roles of the JNK pathway in proapoptosis signaling have been demonstrated by knockout mouse studies. Mice lacking the JNK3 gene were reported to exhibit marked reduction in excitotoxicity-induced apoptosis of hippocampal neurons . JNK2 was shown to be required for apoptosis of immature thymocytes induced by anti-CD3 antibody but not for activationinduced cell death of mature T cells (Sabapathy et al., 1999). Compound mutant mice lacking the JNK1 and JNK2 genes suggested that JNK1 and JNK2 regulate region-specific apoptosis during early brain development (Kuan et al., 1999). Several lines of evidence have also suggested the pro-apoptotic roles of the p38 pathway (Xia et al., 1995;Kawasaki et al., 1997;Harper and LoGrasso et al., 2001), although they have not yet been supported by data of mice deficient for the p38 genes.Apoptosis signal-regulating kinase 1 (ASK1)/MAPKKK5 is a ubiquitously expressed MAPKKK that activates the JNK and p38 pathways by directly phosphorylating and thereby activating their respective MAPKKs, MKK4 (SEK1)/MKK7 and MKK3/MKK6 Ichijo et al., 1997) (Fig. 1). Overexpression of wild-type or constitutively active ASK1 induces apop...

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Signalling for survival and death in neurones: the role of stress-activated kinases, JNK and p38

Cited by 282 publications

References 147 publications

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons

Roles of MAPKKK ASK1 in Stress-Induced Cell Death.

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