Mitogen-Activated Protein Kinase p38 Controls the Expression and Posttranslational Modification of Tristetraprolin, a Regulator of Tumor Necrosis Factor Alpha mRNA Stability

Mahtani, Kamal R; Brook, Matthew; Dean, Jonathan L. E.; Sully, Gareth; Saklatvala, Jeremy; Clark, Andrew R.

doi:10.1128/mcb.21.9.6461-6469.2001

Cited by 415 publications

(458 citation statements)

References 58 publications

(82 reference statements)

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“…Several investigators demonstrated that PD98059, an inhibitor of MEK, suppressed TNF␣ production in LPS-stimulated or CD154-stimulated monocytes (36)(37)(38)(39). Conversely, it has been reported that p38 is involved not only in the translation, but also in the stabilization of TNF␣ mRNA (40)(41)(42). These findings are in accordance with the results of the present study, that activation of both ERK and p38 is important for TNF␣ production by CD154 plus IFN␥-stimulated CD14ϩ synovial cells and for ex vivo TNF␣ production by freshly isolated synovial cells from RA patients.…”

Section: Discussionmentioning

confidence: 99%

Amplification of the synovial inflammatory response through activation of mitogen‐activated protein kinases and nuclear factor κB using ligation of CD40 on CD14+ synovial cells from patients with rheumatoid arthritis

Harigai¹,

Hara²,

Kawamoto³

et al. 2004

Arthritis & Rheumatism

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Objective. To determine the signal transduction pathways in CD14؉ synovial cells from patients with rheumatoid arthritis (RA) after CD40 ligation, and to examine their role in amplifying synovial inflammation in affected joints.Methods. Expression of messenger RNA was analyzed using quantitative reverse transcriptionpolymerase chain reaction. Cytokines and chemokines were measured using enzyme-linked immunosorbent assay. Activation of kinases was detected using Western blotting. Nuclear translocation of NF-B was examined using immunohistochemistry. CD14؉ synovial cells were enriched using magnetic cell sorting. Fibroblastlike synoviocytes (FLS) were obtained by passaging primary synovial cell culture.Results. Stimulation of CD14؉ synovial cells from RA patients by recombinant soluble CD154 (rsCD154) significantly induced expression of tumor necrosis factor ␣ (TNF␣),

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Section: Discussionmentioning

confidence: 99%

Amplification of the synovial inflammatory response through activation of mitogen‐activated protein kinases and nuclear factor κB using ligation of CD40 on CD14+ synovial cells from patients with rheumatoid arthritis

Harigai¹,

Hara²,

Kawamoto³

et al. 2004

Arthritis & Rheumatism

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“…This substrate, along with its closely related family member MK3 (3pk), were both shown to activate various substrates including small heat shock protein 27 (HSP27) [53], lymphocyte-specific protein 1 (LSP1) [54], cAMP response element-binding protein (CREB) [55], transcription factor ATF1 [55], SRF [56], and tyrosine hydroxylase [57]. More recently, MK2 has been found to phosphorylate tristetraprolin (TTP), a protein that is known www.cell-research.com | Cell Research, 15(1): 11-18, Jan 2005 to destabilize mRNA hinting at a role for p38 in mRNA stability [58]. MNK1 is another kinase substrate of p38 whose function is thought to reside in translational initiation due to the observation that MNK1 and MNK2 can phosphorylate eukaryotic initiation factor-4e (eIF-4E) [59,60].…”

Section: Downstream Substrates Of P38 Group Map Kinases Protein Kinasmentioning

confidence: 99%

Activation and signaling of the p38 MAP kinase pathway

2005

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The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.

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“…TTP exists in numerous phosphorylated forms, which suggests that it may be targeted by several signaling pathways. TTP is phosphorylated by the mitogen-activated protein kinase (MAPK) p42, the p38 MAPK, and MAPK-activated protein kinase 2 (Taylor et al, 1995;Carballo et al, 2001;Mahtani et al, 2001). TTP binds to 14-3-3 proteins, the binding being largely dependent upon a specific site in the TTP C terminus, and the interaction between TTP and 14-3-3 proteins is biologically significant in determining cytoplasmic localization.…”

Section: Tristetraprolinmentioning

confidence: 99%

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

294

259

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Recent evidence suggests that gene expression may be regulated, at least in part, at post-transcriptional level by factors inducing the extremely rapid degradation of messenger RNAs. These factors include reactions between adenyl-uridyl-rich elements (AREs) of the relevant mRNA and either specific proteins that bind to these elements or exosomes. This review deals with examples of the proteins (AU-rich binding proteins, AUBPs) and exosomes, which have been shown to form complexes with AREs and bring about rapid degradation of the relevant mRNA, and with certain other factors, which protect the RNA from such degradation. The biochemical and physiological factors underlying the stability of messenger RNAs carrying the ARE motifs will be reviewed in the light of their emerging significance for cell physiology, human pathology, and molecular medicine. We also consider the possible application of the results of recent insights into the mechanisms to pharmacological interventions to prevent or cure disorders, especially developmental disorders, which the suppression of gene expression may bring about. Molecular targeting of specific steps in protein degradation by synthetic compounds has already been utilized for the development of pharmacological therapies.

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Mitogen-Activated Protein Kinase p38 Controls the Expression and Posttranslational Modification of Tristetraprolin, a Regulator of Tumor Necrosis Factor Alpha mRNA Stability

Cited by 415 publications

References 58 publications

Amplification of the synovial inflammatory response through activation of mitogen‐activated protein kinases and nuclear factor κB using ligation of CD40 on CD14+ synovial cells from patients with rheumatoid arthritis

Amplification of the synovial inflammatory response through activation of mitogen‐activated protein kinases and nuclear factor κB using ligation of CD40 on CD14+ synovial cells from patients with rheumatoid arthritis

Activation and signaling of the p38 MAP kinase pathway

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

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