Reactive Oxygen Species Promote TNFα-Induced Death and Sustained JNK Activation by Inhibiting MAP Kinase Phosphatases

Kamata, Hideaki; Honda, Shi-ichi; Maeda, Shin; Chang, Louise; Hirata, Hajime; Karin, Michael

doi:10.1016/j.cell.2004.12.041

Cited by 1,688 publications

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“…Mitogen activated protein kinase phosphatases (MKP) also have a reactive cysteine, required for catalytic activity, and oxidation of the cysteine in MKPs result in inactivation of the phosphatase activity, leading to enhanced activation of MAPKs, including JNK and ERK [129][130][131]. The enhanced activation of protein kinases as a result of inactivation of the phosphatases represents one mechanism whereby H 2 O 2 -associated oxidations enhance signaling by RTKs.…”

Section: Regulation Of Tyrosine Phosphatasesmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

705

652

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Section: Regulation Of Tyrosine Phosphatasesmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

705

652

View full text Add to dashboard Cite

“…[14][15][16] Indeed, antioxidant treatment can afford near-complete protection against killing caused by stimulation of TNF-Rs in various cell types. 14,15 Interestingly, ROS-induced cytotoxicity is mediated through activation of the JNK pathway, 14,16 and sustained activation of this pathway by TNFa depends in fact on ROS . [14][15][16] Thus, the activities of ROS and JNK seem to participate in the same death-inducing mechanism triggered by TNF-Rs.…”

Section: Involvement Of Ros In the Induction Of Jnk And Pcd Downstreamentioning

confidence: 99%

NF-κB meets ROS: an ‘iron-ic’ encounter

et al. 2005

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“…CREB may be phosphorylated by kinases [53] that are induced by M-CSF, such as PI-3K [63], or PKA induced by LPS [64]. However, CREB has recently been found to be phosphorylated downstream of p38 [65], and CREB can also be phosphorylated downstream of ERK1/2. In both cases, CREB is not phosphorylated directly by MAPK, but by MSK1/2, kinases activated by either the ERK1/2 or p38 MAPK [25,26,66].…”

mentioning

confidence: 99%

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

et al. 2009

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MAPK phosphatase-1 (MKP-1) is a protein phosphatase that plays a crucial role in innate immunity. This phosphatase inactivates ERK1/2, which are involved in two opposite functional activities of the macrophage, namely proliferation and activation. Here we found that although macrophage proliferation and activation induce MKP-1 with different kinetics, gene expression is mediated by the proximal promoter sequences localized between À380 and À180 bp. Mutagenesis experiments of the proximal element determined that CRE/AP-1 is required for LPS-or M-CSF-induced activation of the MKP-1 gene. Moreover, the results from gel shift analysis and chromatin immunoprecipitation indicated that c-Jun and CREB bind to the CRE/AP-1 box. The distinct kinetics shown by M-CSF and LPS correlates with the induction of JNK and c-jun, as well as the requirement for Raf-1. The signal transduction pathways that activate the induction of MKP-1 correlate kinetically with induction by M-CSF and LPS.Key words: Activation . Kinases . Macrophage . Phosphatases . Proliferation IntroductionMacrophages perform critical functions during the immune response. These cells are regulators of homeostasis and play an important role in innate and acquired immunity during infection, tumor growth, and wound healing [1]. In response to needs, tissue macrophages proliferate, further differentiate to more specialized macrophagic populations, or become activated. Macrophages, like many other cells of the immune system, are produced in large excess and most undergo apoptosis [2].In the presence of M-CSF, macrophages differentiate and proliferate. However, the proliferation of these cells is blocked when they are activated by Gram-negative LPS or by . Activation causes many biochemical, morphological and functional modifications. Macrophage response to M-CSF and LPS involves the phosphorylation of the three members of the MAPK family [4].MAPK are critical components of signal transduction pathways activated by a range of stimuli and they mediate a number of physiological and pathological changes in cell function [5,6]. MAPK activation requires phosphorylation on a threonine and tyrosine residue located in the activation loop. This process is reversible even in the continued presence of activating stimuli, thereby indicating that protein phosphatases regulate MAPK [7]. Although MAPK are conserved evolutionary pathways present in eukaryotic cells, the kinetics of activation and their subcellular compartmentalization are cell type-specific, and they orchestrate differential cellular responses. For example, in neuronal cells, sustained MAPK phosphorylation of even days is required for cellular activation or differentiation, while in fibroblasts, phosphorylation of this kinase family is very short. In contrast, to Immunol. 2009. 39: 1902-1913 Cristina Casals-Casas et al. 1902 achieve proliferation, extended activation of MAPK is required in these cells [6,7]. The correct spatio-temporal regulation of MAPK signalling is crucial in determining cellular responses to g...

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Reactive Oxygen Species Promote TNFα-Induced Death and Sustained JNK Activation by Inhibiting MAP Kinase Phosphatases

Cited by 1,688 publications

References 52 publications

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

NF-κB meets ROS: an ‘iron-ic’ encounter

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

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