| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 275, Issue 11, 7818-7825, March 17, 2000
From the We have found that lethal toxin from
Clostridium sordellii, which specifically inactivates the
low molecular weight G proteins Ras, Rap, and Rac, inhibits the
activation of p38 mitogen-activated protein kinase (MAPK) by
interleukin-1 (IL-1) in EL4.NOB-1 cells and primary fibroblasts. The
target protein involved appeared to be Ras, because transient
transfections with dominant negative RasN17 inhibited p38 MAPK
activation by IL-1. Furthermore, transfections of cells with
constitutively active RasVHa-activated p38 MAPK. Further evidence for
Ras involvement came from the observation that IL-1 caused a rapid
activation of Ras in the cells and from the inhibitory effects of the
Ras inhibitors manumycin A and damnacanthal. Toxin B from
Clostridium difficile, which inactivates Rac, Cdc42, and
Rho, was without effect. Dominant negative versions of Rac (RacN17) or
Rap (Rap1AN17) did not inhibit the response. Intriguingly, transfection
of cells with dominant negative Rap1AN17 activated p38 MAPK.
Furthermore, constitutively active Rap1AV12 inhibited p38 MAPK
activation by IL-1, consistent with Rap antagonizing Ras function. IL-1
also activated Rap in the cells, but with slower kinetics than Ras. Our
studies therefore provide clear evidence using multiple approaches for
Ras as a signaling component in the activation of p38 MAPK by IL-1,
with Rap having an inhibitory effect.
Divergent Roles for Ras and Rap in the Activation of p38
Mitogen-activated Protein Kinase by Interleukin-1*
,
Department of Biochemistry, Biotechnology
Institute, Trinity College, Dublin 2, Ireland, the
§ Unité des Toxines Microbiennes, Institut Pasteur,
25 Rue Docteur Roux, 75724 Paris, Cedex 15, France, and the
¶ Microbiology & Tumorbiology Centre, Box 280, Karolinska
Institutet, S-171 77 Stockholm, Sweden
*
This work was supported by grants from the Health Research
Board Ireland, Enterprise Ireland, and the European Union.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.:
353-1-6082439; Fax: 353-1-6772400; E-mail: laoneill@tcd.ie.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. H. Diks, K. Kok, T. O'Toole, D. W. Hommes, P. van Dijken, J. Joore, and M. P. Peppelenbosch Kinome Profiling for Studying Lipopolysaccharide Signal Transduction in Human Peripheral Blood Mononuclear Cells J. Biol. Chem., November 19, 2004; 279(47): 49206 - 49213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mansell, E. Brint, J. A. Gould, L. A. O'Neill, and P. J. Hertzog Mal Interacts with Tumor Necrosis Factor Receptor-associated Factor (TRAF)-6 to mediate NF-{kappa}B Activation by Toll-like Receptor (TLR)-2 and TLR4 J. Biol. Chem., September 3, 2004; 279(36): 37227 - 37230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-C. Chen, Y.-S. Chang, J.-C. Kang, M.-J. Hsu, J.-R. Sheu, T.-L. Chen, C.-M. Teng, and C.-H. Lin Peptidoglycan Induces Nuclear Factor-{kappa}B Activation and Cyclooxygenase-2 Expression via Ras, Raf-1, and ERK in RAW 264.7 Macrophages J. Biol. Chem., May 14, 2004; 279(20): 20889 - 20897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xu, H. An, Y. Yu, M. Zhang, R. Qi, and X. Cao Ras Participates in CpG Oligodeoxynucleotide Signaling through Association with Toll-like Receptor 9 and Promotion of Interleukin-1 Receptor-associated Kinase/Tumor Necrosis Factor Receptor-associated Factor 6 Complex Formation in Macrophages J. Biol. Chem., September 19, 2003; 278(38): 36334 - 36340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. MacGillivray, M. T. Herrera-Abreu, C.-W. Chow, C. Shek, Q. Wang, E. Vachon, G.-S. Feng, K. A. Siminovitch, C. A. G. McCulloch, and G. P. Downey The Protein Tyrosine Phosphatase SHP-2 Regulates Interleukin-1-induced ERK Activation in Fibroblasts J. Biol. Chem., July 11, 2003; 278(29): 27190 - 27198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ling, T. Zhu, and P. E. Lobie Src-CrkII-C3G-dependent Activation of Rap1 Switches Growth Hormone-stimulated p44/42 MAP Kinase and JNK/SAPK Activities J. Biol. Chem., July 11, 2003; 278(29): 27301 - 27311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Sanz-Moreno, B. Casar, and P. Crespo p38{alpha} Isoform Mxi2 Binds to Extracellular Signal-Regulated Kinase 1 and 2 Mitogen-Activated Protein Kinase and Regulates Its Nuclear Activity by Sustaining Its Phosphorylation Levels Mol. Cell. Biol., May 1, 2003; 23(9): 3079 - 3090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Yoshino, Y. Osuga, Y. Hirota, K. Koga, T. Hirata, T. Yano, T. Ayabe, O. Tsutsumi, and Y. Taketani Endometrial Stromal Cells Undergoing Decidualization Down-Regulate Their Properties to Produce Proinflammatory Cytokines in Response to Interleukin-1{beta} via Reduced p38 Mitogen-Activated Protein Kinase Phosphorylation J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2236 - 2241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Dunne and L. A. J. O'Neill The Interleukin-1 Receptor/Toll-Like Receptor Superfamily: Signal Transduction During Inflammation and Host Defense Sci. Signal., February 25, 2003; 2003(171): re3 - re3. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Caron Cellular functions of the Rap1 GTP-binding protein: a pattern emerges J. Cell Sci., February 1, 2003; 116(3): 435 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Brint, K. A. Fitzgerald, P. Smith, A. J. Coyle, J.-C. Gutierrez-Ramos, P. G. Fallon, and L. A. J. O'Neill Characterization of Signaling Pathways Activated by the Interleukin 1 (IL-1) Receptor Homologue T1/ST2. A ROLE FOR JUN N-TERMINAL KINASE IN IL-4 INDUCTION J. Biol. Chem., December 13, 2002; 277(51): 49205 - 49211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. D. Martin, P. E. Lonergan, B. Boland, M. P. Fogarty, M. Brady, D. F. Horrobin, V. A. Campbell, and M. A. Lynch Apoptotic Changes in the Aged Brain Are Triggered by Interleukin-1beta -induced Activation of p38 and Reversed by Treatment with Eicosapentaenoic Acid J. Biol. Chem., September 6, 2002; 277(37): 34239 - 34246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Fujita, T. Meguro, R. Fukuyama, H. Nakamuta, and M. Koida New Signaling Pathway for Parathyroid Hormone and Cyclic AMP Action on Extracellular-regulated Kinase and Cell Proliferation in Bone Cells. CHECKPOINT OF MODULATION BY CYCLIC AMP J. Biol. Chem., June 14, 2002; 277(25): 22191 - 22200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Vasselon and P. A. Detmers Toll Receptors: a Central Element in Innate Immune Responses Infect. Immun., March 1, 2002; 70(3): 1033 - 1041. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Vasselon, W. A Hanlon, S. D Wright, and P. A. Detmers Toll-like receptor 2 (TLR2) mediates activation of stress-activated MAP kinase p38 J. Leukoc. Biol., March 1, 2002; 71(3): 503 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. McDermott and L. A. J. O'Neill Ras Participates in the Activation of p38 MAPK by Interleukin-1 by Associating with IRAK, IRAK2, TRAF6, and TAK-1 J. Biol. Chem., March 1, 2002; 277(10): 7808 - 7815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Qa'Dan, L. M. Spyres, and J. D. Ballard pH-Enhanced Cytopathic Effects of Clostridium sordellii Lethal Toxin Infect. Immun., September 1, 2001; 69(9): 5487 - 5493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. J. O'Neill The Interleukin-1 Receptor/Toll-like Receptor Superfamily: Signal Transduction During Inflammation and Host Defense Sci. Signal., August 8, 2000; 2000(44): re1 - re1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. McMahon, C. Stenson, F. McPhillips, A. Fanning, H. R. Brady, and C. Godson Lipoxin A4 Antagonizes the Mitogenic Effects of Leukotriene D4 in Human Renal Mesangial Cells. DIFFERENTIAL ACTIVATION OF MAP KINASES THROUGH DISTINCT RECEPTORS J. Biol. Chem., September 1, 2000; 275(36): 27566 - 27575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Schmitt and P. J. S. Stork beta 2-Adrenergic Receptor Activates Extracellular Signal-regulated Kinases (ERKs) via the Small G Protein Rap1 and the Serine/Threonine Kinase B-Raf J. Biol. Chem., August 11, 2000; 275(33): 25342 - 25350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Caunt, E. Kiss-Toth, F. Carlotti, R. Chapman, and E. E. Qwarnstrom Ras Controls Tumor Necrosis Factor Receptor-associated Factor (TRAF)6-dependent Induction of Nuclear Factor-kappa B. SELECTIVE REGULATION THROUGH RECEPTOR SIGNALING COMPONENTS J. Biol. Chem., February 23, 2001; 276(9): 6280 - 6288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Madrid, M. W. Mayo, J. Y. Reuther, and A. S. Baldwin Jr. Akt Stimulates the Transactivation Potential of the RelA/p65 Subunit of NF-kappa B through Utilization of the Ikappa B Kinase and Activation of the Mitogen-activated Protein Kinase p38 J. Biol. Chem., May 25, 2001; 276(22): 18934 - 18940. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
