|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 275, Issue 18, 13297-13306, May 5, 2000
From the Cytokine Research Section, Department of Bioimmunotherapy,
The University of Texas M. D. Anderson Cancer Center,
Houston, Texas 77030
Ceramide has been implicated as an intermediate
in the signal transduction of several cytokines including tumor
necrosis factor (TNF). Both ceramide and TNF activate a wide variety of
cellular responses, including NF-
Protein Tyrosine Kinase p56lck Is
Required for Ceramide-induced but Not Tumor Necrosis Factor-induced
Activation of NF-
B, AP-1, JNK, and Apoptosis*
, and
B, AP-1, JNK, and apoptosis.
Whether ceramide transduces these signals through the same mechanism as TNF is not known. In the present study we investigated the role of the
T cell-specific tyrosine kinase p56lck in
ceramide- and TNF-mediated cellular responses by comparing the
responses of Jurkat T cells with JCaM1 cells, isogeneic Lck-deficient T
cells. Treatment with ceramide activated NF-B, degraded IB
, and induced NF-B-dependent reporter gene expression in a
time-dependent manner in Jurkat cells but not in JCaM1
cells, suggesting the critical role of p56lck
kinase. These effects were specific to ceramide, as activation of
NF-B by phorbol 12-myristate 13-acetate, lipopolysaccharide, H2O2, and TNF was minimally affected.
p56lck was also found to be required for
ceramide-induced but not TNF-induced AP-1 activation. Similarly,
ceramide activated the protein kinases JNK and mitogen-activated
protein kinase kinase in Jurkat cells but not in JCaM1 cells. Ceramide
also induced cytotoxicity and activated caspases and reactive oxygen
intermediates in Jurkat cells but not in JCaM1 cells. Ceramide
activated p56lck activity in Jurkat cells.
Moreover, the reconstitution of JCaM1 cells with
p56lck tyrosine kinase reversed the
ceramide-induced NF-B activation and cytotoxicity. Overall our
results demonstrate that p56lck plays a
critical role in the activation of NF-B, AP-1, JNK, and apoptosis by
ceramide but has minimal or no role in activation of these responses by
TNF.
*
This work was supported by a grant from the Clayton
Foundation of Research.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.
Recipient of a foreign component of the DBT National
Associateship, Government of India, Permanent address: R. D. College, Sheikhpura 811105, India.
§
To whom correspondence should be addressed: Cytokine Research
Section, Dept. of Bioimmunotherapy, Box 143, The University of Texas
M. D. Anderson Cancer Center, 1515 Holcombe Blvd.,
Houston, TX 77030. Tel.: 713-792-3503/6459; Fax: 713-794-1613;
E-mail: aggarwal@utmdacc.mda.uth.tmc.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  L. W. Maines, K. J. French, E. B. Wolpert, D. A. Antonetti, and C. D. Smith Pharmacologic Manipulation of Sphingosine Kinase in Retinal Endothelial Cells: Implications for Angiogenic Ocular Diseases Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5022 - 5031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kajimoto, Y. Shirai, N. Sakai, T. Yamamoto, H. Matsuzaki, U. Kikkawa, and N. Saito Ceramide-induced Apoptosis by Translocation, Phosphorylation, and Activation of Protein Kinase C{delta} in the Golgi Complex J. Biol. Chem., March 26, 2004; 279(13): 12668 - 12676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-G. Hur, Y. Yun, and J. Won Rosmarinic Acid Induces p56lck-Dependent Apoptosis in Jurkat and Peripheral T Cells via Mitochondrial Pathway Independent from Fas/Fas Ligand Interaction J. Immunol., January 1, 2004; 172(1): 79 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takada, A. Mukhopadhyay, G. C. Kundu, G. H. Mahabeleshwar, S. Singh, and B. B. Aggarwal Hydrogen Peroxide Activates NF-{kappa}B through Tyrosine Phosphorylation of I{kappa}B{alpha} and Serine Phosphorylation of p65: EVIDENCE FOR THE INVOLVEMENT OF I{kappa}B{alpha} KINASE AND Syk PROTEIN-TYROSINE KINASE J. Biol. Chem., June 20, 2003; 278(26): 24233 - 24241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Budagian, E. Bulanova, L. Brovko, Z. Orinska, R. Fayad, R. Paus, and S. Bulfone-Paus Signaling through P2X7 Receptor in Human T Cells Involves p56lck, MAP Kinases, and Transcription Factors AP-1 and NF-kappa B J. Biol. Chem., January 10, 2003; 278(3): 1549 - 1560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ashikawa, S. Majumdar, S. Banerjee, A. C. Bharti, S. Shishodia, and B. B. Aggarwal Piceatannol Inhibits TNF-Induced NF-{kappa}B Activation and NF-{kappa}B-Mediated Gene Expression Through Suppression of I{kappa}B{alpha} Kinase and p65 Phosphorylation J. Immunol., December 1, 2002; 169(11): 6490 - 6497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Majumdar, B. Lamothe, and B. B. Aggarwal Thalidomide Suppresses NF-{kappa}B Activation Induced by TNF and H2O2, But Not That Activated by Ceramide, Lipopolysaccharides, or Phorbol Ester J. Immunol., March 15, 2002; 168(6): 2644 - 2651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. SIGNORELLI, C. LUBERTO, and Y. A. HANNUN Ceramide inhibition of NF-{kappa}B activation involves reverse translocation of classical protein kinase C (PKC) isoenzymes: requirement for kinase activity and carboxyl-terminal phosphorylation of PKC for the ceramide response FASEB J, November 1, 2001; 15(13): 2401 - 2414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nees, J. M. Geoghegan, T. Hyman, S. Frank, L. Miller, and C. D. Woodworth Papillomavirus Type 16 Oncogenes Downregulate Expression of Interferon-Responsive Genes and Upregulate Proliferation-Associated and NF-{kappa}B-Responsive Genes in Cervical Keratinocytes J. Virol., May 1, 2001; 75(9): 4283 - 4296. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Rudner, A. Lepple-Wienhues, W. Budach, J. Berschauer, B. Friedrich, S. Wesselborg, K. Schulze-Osthoff, and C. Belka Wild-type, mitochondrial and ER-restricted Bcl-2 inhibit DNA damage-induced apoptosis but do not affect death receptor-induced apoptosis J. Cell Sci., January 12, 2001; 114(23): 4161 - 4172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. D. Kolodgie, A. Farb, and R. Virmani Local Delivery of Ceramide for Restenosis : Is There a Future for Lipid Therapy? Circ. Res., August 18, 2000; 87(4): 264 - 267. [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 |