Home LiteratureArticle Details
PMID: 12776182 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The role of the death-domain kinase RIP in tumour-necrosis-factor-induced activation of mitogen-activated protein kinases.

EMBO reports ·Vol. 4 ·No. 6 ·2003-06-00 ·Pages 623-7

Devin A, Lin Y, Liu ZG

Abstract

The death-domain kinase RIP (receptor-interacting protein) is an important effector of tumour necrosis factor (TNF) signalling and is essential for TNF-induced nuclear factor-kappaB activation. However, the function of RIP in the TNF-induced activation of mitogen-activated protein kinases (MAPKs) has not been fully investigated. In this report, using Rip null (Rip(-/-)) mouse fibroblast cells, we investigated whether RIP is required for TNF-induced activation of the MAPKs extracellular-signal-related kinase (ERK), p38 and c-Jun amino-terminal kinase (JNK). We found that TNF-induced activation of ERK, p38 and JNK is decreased in Rip(-/-) cells. The activation of these kinases by interleukin-1 is normal in Rip(-/-) cells. More importantly, we showed that the kinase activity of RIP is needed for ERK activation.

MeSH Terms
Animals Blotting, Western Enzyme Activation Fibroblasts/metabolism Humans Interleukin-1/metabolism JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 4 MAP Kinase Signaling System Mice Mice, Transgenic Mitogen-Activated Protein Kinase Kinases/metabolism Mitogen-Activated Protein Kinases/metabolism NF-kappa B/metabolism Plasmids/metabolism Protein Structure, Tertiary Proteins/genetics,metabolism,physiology Receptor-Interacting Protein Serine-Threonine Kinases Transfection Tumor Necrosis Factor-alpha/metabolism p38 Mitogen-Activated Protein Kinases
Chemicals
Interleukin-1 NF-kappa B Proteins Tumor Necrosis Factor-alpha RIPK1 protein, human Receptor-Interacting Protein Serine-Threonine Kinases Ripk1 protein, mouse JNK Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases MAP Kinase Kinase 4 Mitogen-Activated Protein Kinase Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Devin Anne
Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Lin Yong
Liu Zheng-gang
References (24)
24 references, click to expand
  1. Cellular responses to tumor necrosis factor.
    Curr Issues Mol Biol. 2001 Oct;3(4):79-90 PMID: 11719971
  2. Cloning and expression of cDNAs for two distinct murine tumor necrosis factor receptors demonstrate one receptor is species specific.
    Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2830-4 PMID: 1849278
  3. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal.
    Immunity. 1998 Mar;8(3):297-303 PMID: 9529147
  4. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule.
    Nat Immunol. 2000 Dec;1(6):489-95 PMID: 11101870
  5. Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain.
    Genes Dev. 1999 May 15;13(10):1297-308 PMID: 10346818
  6. Tumor necrosis factor, other cytokines and disease.
    Annu Rev Cell Biol. 1993;9:317-43 PMID: 8280464
  7. MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation.
    Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7272-7 PMID: 10852963
  8. RIP mediates tumor necrosis factor receptor 1 activation of NF-kappaB but not Fas/APO-1-initiated apoptosis.
    EMBO J. 1996 Nov 15;15(22):6189-96 PMID: 8947041
  9. Tumor necrosis factor alpha-induced activation of c-jun N-terminal kinase is mediated by TRAF2.
    EMBO J. 1997 Mar 3;16(5):1080-92 PMID: 9118946
  10. Mitogen-activated protein kinase cascades as regulators of stress responses.
    Ann N Y Acad Sci. 1998 Jun 30;851:139-46 PMID: 9668616
  11. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex.
    Immunity. 1996 Apr;4(4):387-96 PMID: 8612133
  12. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways.
    Cell. 1996 Jan 26;84(2):299-308 PMID: 8565075
  13. Signal transduction by the c-Jun N-terminal kinase.
    Biochem Soc Symp. 1999;64:1-12 PMID: 10207617
  14. TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40.
    Science. 1995 Sep 8;269(5229):1424-7 PMID: 7544915
  15. The Fas death factor.
    Science. 1995 Mar 10;267(5203):1449-56 PMID: 7533326
  16. Two tumour necrosis factor receptors: structure and function.
    Trends Cell Biol. 1995 Oct;5(10):392-9 PMID: 14732063
  17. MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration.
    Proc Natl Acad Sci U S A. 2000 May 9;97(10):5243-8 PMID: 10805784
  18. Two TNF receptors.
    Immunol Today. 1992 May;13(5):151-3 PMID: 1322675
  19. RICK/Rip2/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems.
    Nature. 2002 Mar 14;416(6877):194-9 PMID: 11894098
  20. Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappaB activation prevents cell death.
    Cell. 1996 Nov 1;87(3):565-76 PMID: 8898208
  21. ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis.
    EMBO Rep. 2001 Mar;2(3):222-8 PMID: 11266364
  22. RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death.
    Cell. 1995 May 19;81(4):513-23 PMID: 7538908
  23. Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice.
    Immunity. 1997 Nov;7(5):715-25 PMID: 9390694
  24. The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation.
    Immunity. 2000 Apr;12(4):419-29 PMID: 10795740
Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1038/sj.embor.embor854
Published
2003-06-00
Pages
623-7
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1319199
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.embor.embor854 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2