論文 - 詳細
| RRC ID | 67980 |
|---|---|
| 著者 | Matsuguchi T, Musikacharoen T, Johnson TR, Kraft AS, Yoshikai Y. |
| タイトル | A novel mitogen-activated protein kinase phosphatase is an important negative regulator of lipopolysaccharide-mediated c-Jun N-terminal kinase activation in mouse macrophage cell lines. |
| ジャーナル | Mol Cell Biol |
| Abstract |
We have isolated a cDNA homologous to known dual-specificity phosphatases from a mouse macrophage cDNA library and termed it MKP-M (for mitogen-activated protein kinase phosphatase isolated from macrophages). Three other presumed splice variant isoforms have also been identified for MKP-M. The longest and most abundant mRNA contains an open reading frame corresponding to 677 amino acids and produces an 80-kDa protein. The deduced amino acid sequence of MKP-M is most similar to those of hVH-5 (or mouse M3/6) and VHP1, a Caenorhabditis elegans tyrosine phosphatase. It includes an N-terminal rhodanase homology domain, the extended active-site sequence motif (V/L)X(V/I)HCXAG(I/V)SRSXT(I/V)XXAY(L/I)M (where X is any amino acid), and a C-terminal PEST sequence. Northern blot analysis revealed a dominant MKP-M mRNA species of approximately 5.5 kb detected ubiquitously among all tissues examined. MKP-M was constitutively expressed in mouse macrophage cell lines, and its expression levels were rapidly increased by lipopolysaccharide (LPS) stimulation but not by tumor necrosis factor alpha (TNF-alpha), gamma interferon, interleukin-2 (IL-2), or IL-15 stimulation. Immunocytochemical analysis showed MKP-M to be present within cytosol. When expressed in COS7 cells, MKP-M blocks activation of mitogen-activated protein kinases with the selectivity c-Jun N-terminal kinase (JNK) >> p38 = extracellular signal-regulated kinase. Furthermore, expression of a catalytically inactive form of MKP-M in a mouse macrophage cell line increased the intensity and duration of JNK activation and TNF-alpha secretion after LPS stimulation, suggesting that MKP-M is at least partially responsible for the desensitization of LPS-mediated JNK activation and cytokine secretion in macrophages. |
| 巻・号 | 21(20) |
| ページ | 6999-7009 |
| 公開日 | 2001-10-1 |
| DOI | 10.1128/MCB.21.20.6999-7009.2001 |
| PMID | 11564882 |
| PMC | PMC99875 |
| MeSH | Amino Acid Sequence Animals Blotting, Northern COS Cells Catalysis Cell Line DNA, Complementary / metabolism Down-Regulation Dual-Specificity Phosphatases Enzyme Activation Enzyme-Linked Immunosorbent Assay Escherichia coli / metabolism Gene Expression Regulation, Enzymologic Gene Library Genes, Dominant Humans Immunoblotting Immunohistochemistry Interferon-gamma / pharmacology Interleukin-15 / pharmacology Interleukin-2 / pharmacology JNK Mitogen-Activated Protein Kinases Lipopolysaccharides / metabolism* MAP Kinase Signaling System* Macrophages / enzymology* Mice Mitogen-Activated Protein Kinase Phosphatases Mitogen-Activated Protein Kinases / metabolism* Models, Genetic Molecular Sequence Data Phosphoric Monoester Hydrolases / chemistry* Phosphoric Monoester Hydrolases / metabolism Plasmids / metabolism Precipitin Tests Protein Tyrosine Phosphatases / biosynthesis* Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism* RNA, Messenger / metabolism Recombinant Proteins / metabolism Time Factors Tissue Distribution Transfection Tumor Necrosis Factor-alpha / pharmacology Tyrosine / metabolism p38 Mitogen-Activated Protein Kinases |
| IF | 3.611 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) COS-7(RCB0539) |