Cell Survival Promoted by the Ras-MAPK Signaling Pathway by Transcription-Dependent and -Independent Mechanisms

Bonni, Azad; Brunet, Anne; West, Anne E.; Datta, Sandeep Robert; Takasu, Mari A.; Greenberg, Michael E.

doi:10.1126/science.286.5443.1358

Cited by 1,731 publications

(1,481 citation statements)

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“…Under certain conditions, CREB-induced gene transcription has survival-promoting effects [4] and also plays a critical role in learning and memory processes in different species, from Drosophila to mammals [1,62]. Both ERK and CREB have been implicated in processes of neuronal plasticity [1,62,66,68].…”

Section: Il-1β Interferes With Bdnf-induced Activation Of the Transcrmentioning

confidence: 99%

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

Tong

Balázs

Soi-ampornkul³

et al. 2008

Neurobiology of Aging

181

135

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The expression of IL-1 is elevated in the CNS in diverse neurodegenerative disorders, including Alzheimer's disease. The hypothesis was tested that IL-1β renders neurons vulnerable to degeneration by interfering with BDNF-induced neuroprotection. In trophic support-deprived neurons, IL-1β compromised the PI3-K/Akt pathway-mediated protection by BDNF and suppressed Akt activation. The effect was specific as in addition to Akt, the activation of MAPK/ ERK, but not PLCγ, was decreased. Activation of CREB, a target of these signaling pathways, was severely depressed by IL-1β. As the cytokine did not influence TrkB receptor and PLCγ activation, IL-1β might have interfered with BDNF signaling at the docking step conveying activation to the PI3-K/Akt and Ras/MAPK pathways. Indeed, IL-1β suppressed the activation of the respective scaffolding proteins IRS-1 and Shc; this effect might involve ceramide generation. IL-1-induced interference with BDNF neuroprotection and signal transduction was corrected, in part, by ceramide production inhibitors and mimicked by the cell-permeable C2-ceramide. These results suggest that IL-1β places neurons at risk by interfering with BDNF signaling involving a ceramide-associated mechanism. Keywords IL-1β; BDNF; signal transduction; cortical neuronsInterleukin-1 (IL-1) is a pluripotent proinflammatory cytokine that is a potent activator of host defense responses to infection and injury both in the periphery and the CNS [59]. However, IL-1 can also exacerbate damage in the CNS resulting from acute insults, such as © 2007 Elsevier Inc. All rights reserved. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript cerebral ischemia and trauma, and circumstantial evidence is consistent with a similar role in chronic neurological diseases, such as multiple sclerosis, Parkinson's disease and Alzheimer's disease (AD) [48]. Furthermore, recent genetic studies highlighted the relevance of IL-1 in AD pathogenesis, showing that specific polymorphisms in the IL-1 gene cluster are associated with greatly increased risk for AD, especially for the earlier onset of the disease [23,50]. The view that inflammatory processes play an important role in pathogenesis has been supported by epidemiological studies, showing that certain antiinflammatory drugs result in a slower progression of the disease [2,8,43,77] and in transgenic AD models decrease the number of dystrophic neurites, activated microglia and IL-1 expression [35], although such drugs also modulate the production of the a...

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Section: Il-1β Interferes With Bdnf-induced Activation Of the Transcrmentioning

confidence: 99%

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

Tong

Balázs

Soi-ampornkul³

et al. 2008

Neurobiology of Aging

181

135

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“…For example active ERK1/2 can activate transcription factors [215] and phosphorylate specific effector kinases-the MAPK-activated protein kinases (MAPKAPKs) such as the mitogen-and stress-activated kinase-1 (MSK1) or the pp90 ribosomal S6 kinase (RSK) [197]. RSK phosphorylates the Bcl-2 family member Bad, thereby inhibiting its pro-apoptotic activity [18]. RSK and MSK1 are also potent activators of the cAMP response element binding protein (CREB), a transcription factor for Bcl-2 and, therefore, an important factor for cell survival [51].…”

Section: Map Kinase Signalingmentioning

confidence: 99%

“…This would suggest that active ERK1/2 plays an important role in pro-survival signal transduction processes. Indeed different studies clearly indicate that under certain conditions the activation of ERK1/2 is essential to neuronal survival [18,218]. Furthermore, the activation of Ras, an initiator of the ERK1/2 signaling cascade, has been shown to also activate the phosphoinositol 3-kinase (PI3-kinase)/AKT pathway, another important survival pathway in neurons, demonstrating possible interlinks between different survival signals [129].…”

Section: Map Kinase Signalingmentioning

confidence: 99%

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MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

302

176

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Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

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“…In addition to the role of ERK in proliferation, the Ras-ERK signaling pathway can promote cell survival through transcription-dependent and -independent mechanisms (Bonni et al, 1999). In fact, ERK-deficient pro-B cells are more susceptible to cell death than wild-type pro-B cells and expression of the prosurvival gene Bcl2 is induced by anti-Igβ stimulation of μMT pro-B cells in an ERK-dependent manner (Yasuda et al, 2008).…”

Section: Importance Of Mef2c For B Cell Hematopoiesis In Bone Marrow mentioning

confidence: 99%

MAP Kinase Cascades in Antigen Receptor Signaling and Physiology

Yasuda

2015

Current Topics in Microbiology and Immunology

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Cell Survival Promoted by the Ras-MAPK Signaling Pathway by Transcription-Dependent and -Independent Mechanisms

Cited by 1,731 publications

References 71 publications

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

MAP Kinase Cascades in Antigen Receptor Signaling and Physiology

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