肿瘤坏死因子刺激的 MAP 激酶激活是通过 Rho 家族 GTP 酶信号通路介导的。
TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway.
机构信息
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
出版信息
Genes Dev. 2011 Oct 1;25(19):2069-78. doi: 10.1101/gad.17224711.
Abstract
The biological response to tumor necrosis factor (TNF) involves activation of MAP kinases. Here we report a mechanism of MAP kinase activation by TNF that is mediated by the Rho GTPase family members Rac/Cdc42. This signaling pathway requires Src-dependent activation of the guanosine nucleotide exchange factor Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site (CRIB motif) on mixed-lineage protein kinases (MLKs). We show that this pathway is essential for full MAP kinase activation during the response to TNF. Moreover, this MLK pathway contributes to inflammation in vivo.
摘要
肿瘤坏死因子（TNF）引起的生物反应涉及到 MAP 激酶的激活。在这里，我们报告了 TNF 激活 MAP 激酶的一种机制，该机制是由 Rho GTPase 家族成员 Rac/Cdc42 介导的。这条信号通路需要Src 依赖性地激活鸟苷核苷酸交换因子 Vav，激活 Rac/Cdc42，并使混合谱系蛋白激酶（MLKs）上的 Rac/Cdc42 相互作用位点（CRI 基序）结合。我们表明，在对 TNF 的反应过程中，该途径对于完全的 MAP 激酶激活是必不可少的。此外，该 MLK 途径有助于体内炎症。
相似文献
1
TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway.肿瘤坏死因子刺激的 MAP 激酶激活是通过 Rho 家族 GTP 酶信号通路介导的。
Genes Dev. 2011 Oct 1;25(19):2069-78. doi: 10.1101/gad.17224711.
2
The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis.MLK家族在神经元凋亡中介导c-Jun氨基末端激酶激活。
Mol Cell Biol. 2001 Jul;21(14):4713-24. doi: 10.1128/MCB.21.14.4713-4724.2001.
3
Activation of the small GTPase Cdc42 by the inflammatory cytokines TNF(alpha) and IL-1, and by the Epstein-Barr virus transforming protein LMP1.炎症细胞因子TNF（α）和IL-1以及爱泼斯坦-巴尔病毒转化蛋白LMP1对小GTP酶Cdc42的激活作用。
J Cell Sci. 1999 Sep;112 ( Pt 17):2983-92. doi: 10.1242/jcs.112.17.2983.
4
An essential role for Rac/Cdc42 GTPases in cerebellar granule neuron survival.Rac/Cdc42 GTP酶在小脑颗粒神经元存活中起重要作用。
J Biol Chem. 2001 Oct 19;276(42):39123-31. doi: 10.1074/jbc.M103959200. Epub 2001 Aug 16.
5
Vav transformation requires activation of multiple GTPases and regulation of gene expression.Vav转化需要多种GTP酶的激活和基因表达的调控。
Mol Cancer Res. 2004 Dec;2(12):702-11.
6
7
Src kinase regulates the activation of a novel FGD-1-related Cdc42 guanine nucleotide exchange factor in the signaling pathway from the endothelin A receptor to JNK.Src激酶在内皮素A受体至JNK的信号通路中调节一种新型FGD-1相关的Cdc42鸟嘌呤核苷酸交换因子的激活。
J Biol Chem. 2003 Aug 8;278(32):29890-900. doi: 10.1074/jbc.M301559200. Epub 2003 May 27.
8
Vav2 as a Rac-GDP/GTP exchange factor responsible for the nectin-induced, c-Src- and Cdc42-mediated activation of Rac.Vav2作为一种Rac-GDP/GTP交换因子，负责nectin诱导的、c-Src和Cdc42介导的Rac激活。
J Biol Chem. 2005 Feb 11;280(6):4940-7. doi: 10.1074/jbc.M408710200. Epub 2004 Oct 13.
9
Epidermal growth factor-dependent regulation of Cdc42 is mediated by the Src tyrosine kinase.表皮生长因子对Cdc42的依赖性调节由Src酪氨酸激酶介导。
J Biol Chem. 2003 Dec 5;278(49):49293-300. doi: 10.1074/jbc.M307021200. Epub 2003 Sep 23.
10
BetaPix-enhanced p38 activation by Cdc42/Rac/PAK/MKK3/6-mediated pathway. Implication in the regulation of membrane ruffling.BetaPix通过Cdc42/Rac/PAK/MKK3/6介导的途径增强p38激活。对膜 ruffling调节的影响。
J Biol Chem. 2001 Jul 6;276(27):25066-72. doi: 10.1074/jbc.M010892200. Epub 2001 Apr 17.
引用本文的文献
1
Unveiling the anti-inflammatory potential of RF16, an interleukin 8-derived therapeutic peptide in macrophages.揭示RF16（一种源自白细胞介素8的巨噬细胞治疗性肽）的抗炎潜力。
J Inflamm (Lond). 2025 Jul 28;22(1):29. doi: 10.1186/s12950-025-00454-w.
2
Mixed lineage kinase (MLK) controls tumor development and angiogenesis.混合谱系激酶（MLK）控制肿瘤发展和血管生成。
Angiogenesis. 2025 May 2;28(3):29. doi: 10.1007/s10456-025-09978-4.
3
Cell-Sonar, a Novel Method for Intracellular Tracking of Secretory Pathways.细胞声纳：一种用于追踪细胞内分泌途径的新方法。
Cells. 2024 Aug 29;13(17):1449. doi: 10.3390/cells13171449.
4
TNF-alpha promotes cilia elongation via mixed lineage kinases signaling in mouse fibroblasts and human RPE-1 cells.肿瘤坏死因子-α通过混合谱系激酶信号通路促进小鼠成纤维细胞和人RPE-1细胞中的纤毛伸长。
Cytoskeleton (Hoboken). 2024 Nov;81(11):639-647. doi: 10.1002/cm.21873. Epub 2024 May 20.
5
TNF-α can promote membrane invasion by activating the MAPK/MMP9 signaling pathway through autocrine in bone-invasive pituitary adenoma.TNF-α 可通过自分泌激活 MAPK/MMP9 信号通路促进侵袭性骨垂体腺瘤的膜侵袭。
CNS Neurosci Ther. 2024 May;30(5):e14749. doi: 10.1111/cns.14749.
6
extracts induce apoptosis of vascular smooth muscle cells via intrinsic and extrinsic pathways.提取物通过内源性和外源性途径诱导血管平滑肌细胞凋亡。
Food Sci Nutr. 2023 Sep 19;11(12):7900-7909. doi: 10.1002/fsn3.3707. eCollection 2023 Dec.
7
Differential co-expression network analysis elucidated genes associated with sensitivity to farnesyltransferase inhibitor and prognosis of acute myeloid leukemia.差异共表达网络分析阐明了与法尼基转移酶抑制剂敏感性和急性髓系白血病预后相关的基因。
Cancer Med. 2023 Dec;12(24):22420-22436. doi: 10.1002/cam4.6804. Epub 2023 Dec 8.
8
Therapeutic potential of natural products in inflammation: underlying molecular mechanisms, clinical outcomes, technological advances, and future perspectives.天然产物在炎症中的治疗潜力：潜在的分子机制、临床结果、技术进展和未来展望。
Inflammopharmacology. 2023 Dec;31(6):2857-2883. doi: 10.1007/s10787-023-01366-y. Epub 2023 Nov 11.
9
USP14 promotes colorectal cancer progression by targeting JNK for stabilization.USP14 通过靶向 JNK 促进结直肠癌的进展。
Cell Death Dis. 2023 Jan 24;14(1):56. doi: 10.1038/s41419-023-05579-5.
10
Mitogen-activated protein kinase kinase 7 in inflammatory, cancer, and neurological diseases.丝裂原活化蛋白激酶激酶7在炎症、癌症和神经疾病中的作用
Front Cell Dev Biol. 2022 Oct 20;10:979673. doi: 10.3389/fcell.2022.979673. eCollection 2022.
本文引用的文献
1
Sam68 is required for both NF-κB activation and apoptosis signaling by the TNF receptor.Sam68 对于 TNF 受体介导的 NF-κB 激活和细胞凋亡信号传导都是必需的。
Mol Cell. 2011 Jul 22;43(2):167-79. doi: 10.1016/j.molcel.2011.05.007. Epub 2011 May 27.
2
TRAF2-MLK3 interaction is essential for TNF-alpha-induced MLK3 activation.TRAF2-MLK3 相互作用对于 TNF-α诱导的 MLK3 激活是必不可少的。
Cell Res. 2010 Jan;20(1):89-98. doi: 10.1038/cr.2009.125. Epub 2009 Nov 17.
3
Acquisition of a potent and selective TC-PTP inhibitor via a stepwise fluorophore-tagged combinatorial synthesis and screening strategy.通过逐步荧光标记组合合成和筛选策略获得一种强效且选择性的 TC-PTP 抑制剂。
J Am Chem Soc. 2009 Sep 16;131(36):13072-9. doi: 10.1021/ja903733z.
4
Riboflavin kinase couples TNF receptor 1 to NADPH oxidase.核黄素激酶将肿瘤坏死因子受体1与NADPH氧化酶联系起来。
Nature. 2009 Aug 27;460(7259):1159-63. doi: 10.1038/nature08206. Epub 2009 Jul 29.
5
Cytokine-induced activation of mixed lineage kinase 3 requires TRAF2 and TRAF6.细胞因子诱导的混合谱系激酶3激活需要TRAF2和TRAF6。
Cell Signal. 2009 Nov;21(11):1620-5. doi: 10.1016/j.cellsig.2009.06.008. Epub 2009 Jul 5.
6
The role of ubiquitin in NF-kappaB regulatory pathways.泛素在核因子-κB调控通路中的作用。
Annu Rev Biochem. 2009;78:769-96. doi: 10.1146/annurev.biochem.78.070907.102750.
7
Induction of hepatitis by JNK-mediated expression of TNF-alpha.通过JNK介导的肿瘤坏死因子-α表达诱导肝炎
Cell. 2009 Jan 23;136(2):249-60. doi: 10.1016/j.cell.2008.11.017.
8
TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death.肿瘤坏死因子诱导的Nox1烟酰胺腺嘌呤二核苷酸磷酸氧化酶激活及其在坏死性细胞死亡诱导中的作用。
Mol Cell. 2007 Jun 8;26(5):675-87. doi: 10.1016/j.molcel.2007.04.021.
9
Chemical genetic analysis of the time course of signal transduction by JNK.JNK信号转导时间进程的化学遗传学分析
Mol Cell. 2006 Mar 3;21(5):701-10. doi: 10.1016/j.molcel.2006.01.018.
10
Analysis of activated GAPs and GEFs in cell lysates.细胞裂解物中活化的GAP和GEF分析。
Methods Enzymol. 2006;406:425-37. doi: 10.1016/S0076-6879(06)06031-9.
Zotero 插件