The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yu, T.-K.
Right arrow Articles by Grimm, E. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yu, T.-K.
Right arrow Articles by Grimm, E. A.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
The Journal of Immunology, 2000, 164: 6244-6251.
Copyright © 2000 by The American Association of Immunologists

IL-2 Activation of NK Cells: Involvement of MKK1/2/ERK But Not p38 Kinase Pathway1

Tse-Kuan Yu, Eva G. Caudell, Christine Smid and Elizabeth A. Grimm2

Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030

IL-2 stimulates extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) in various immune cell populations. The functional roles that these kinases play are still unclear. In this study, we examined whether MAPK kinase (MKK)/ERK and p38 MAPK pathways are necessary for IL-2 to activate NK cells. Using freshly isolated human NK cells, we established that an intact MKK/ERK pathway is necessary for IL-2 to activate NK cells to express at least four known biological responses: LAK generation, IFN-{gamma} secretion, and CD25 and CD69 expression. IL-2 induced ERK activation within 5 min. Treatment of NK cells with a specific inhibitor of MKK1/2, PD98059, during the IL-2 stimulation blocked in a dose-dependent manner each of four sequelae, with inhibition of lymphokine-activated killing induction being least sensitive to MKK/ERK pathway blockade. Activation of p38 MAPK by IL-2 was not detected in NK cells. In contrast to what was observed by others in T lymphocytes, SB203850, a specific inhibitor of p38 MAPK, did not inhibit IL-2-activated NK functions. This data indicate that p38 MAPK activation was not required for IL-2 to activate NK cells for the four functions examined. These results reveal selective signaling differences between NK cells and T lymphocytes; in NK cells, the MKK/ERK pathway and not p38 MAPK plays a critical positive regulatory role during activation by IL-2.




This article has been cited by other articles:


Home page
 Molecular Cancer TherapeuticsHome page
M. A. Bill, C. Bakan, D. M. Benson, Jr., J. Fuchs, G. Young, and G. B. Lesinski
Curcumin induces proapoptotic effects against human melanoma cells and modulates the cellular response to immunotherapeutic cytokines
Mol. Cancer Ther., September 1, 2009; 8(9): 2726 - 2735.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. M. Benson Jr, J. Yu, B. Becknell, M. Wei, A. G. Freud, A. K. Ferketich, R. Trotta, D. Perrotti, R. Briesewitz, and M. A. Caligiuri
Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells
Blood, March 19, 2009; 113(12): 2706 - 2714.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. Sattler, U. Wagner, M. Rossol, J. Sieper, P. Wu, A. Krause, W. A. Schmidt, S. Radmer, S. Kohler, C. Romagnani, et al.
Cytokine-induced human IFN-{gamma}-secreting effector-memory Th cells in chronic autoimmune inflammation
Blood, February 26, 2009; 113(9): 1948 - 1956.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
S. Bessoles, F. Fouret, S. Dudal, G. S. Besra, F. Sanchez, and V. Lafont
IL-2 triggers specific signaling pathways in human NKT cells leading to the production of pro- and anti-inflammatory cytokines
J. Leukoc. Biol., July 1, 2008; 84(1): 224 - 233.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. C. D. Wiseman, L. L. Ma, K. J. Marr, G. J. Jones, and C. H. Mody
Perforin-Dependent Cryptococcal Microbicidal Activity in NK Cells Requires PI3K-Dependent ERK1/2 Signaling
J. Immunol., May 15, 2007; 178(10): 6456 - 6464.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. A. Varker, S. V. Kondadasula, M. R. Go, G. B. Lesinski, R. Ghosh-Berkebile, A. Lehman, J. P. Monk, T. Olencki, K. Kendra, and W. E. Carson III
Multiparametric Flow Cytometric Analysis of Signal Transducer and Activator of Transcription 5 Phosphorylation in Immune Cell Subsets In vitro and following Interleukin-2 Immunotherapy.
Clin. Cancer Res., October 1, 2006; 12(19): 5850 - 5858.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K.-y. Kim, J. K. Kim, S. H. Han, J.-S. Lim, K. I. Kim, D. H. Cho, M.-S. Lee, J.-H. Lee, D.-Y. Yoon, S. R. Yoon, et al.
Adiponectin Is a Negative Regulator of NK Cell Cytotoxicity
J. Immunol., May 15, 2006; 176(10): 5958 - 5964.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. Kawauchi, K. Ihjima, and O. Yamada
IL-2 Increases Human Telomerase Reverse Transcriptase Activity Transcriptionally and Posttranslationally through Phosphatidylinositol 3'-Kinase/Akt, Heat Shock Protein 90, and Mammalian Target of Rapamycin in Transformed NK Cells
J. Immunol., May 1, 2005; 174(9): 5261 - 5269.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
B. Sawitzki, B. Kieselbach, M. Fisser, C. Meisel, K. Vogt, M. Gaestel, M. Lehmann, K. Risch, G. Grutz, and H.-D. Volk
IFN-{gamma} Regulation in Anti-CD4 Antibody-Induced T Cell Unresponsiveness
J. Am. Soc. Nephrol., March 1, 2004; 15(3): 695 - 703.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
V. Lafont, S. Loisel, J. Liautard, S. Dudal, M. Sable-teychene, J.-P. Liautard, and J. Favero
Specific Signaling Pathways Triggered by IL-2 in Human V{gamma}9V{delta}2 T Cells: An Amalgamation of NK and {alpha}{beta} T Cell Signaling
J. Immunol., November 15, 2003; 171(10): 5225 - 5232.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. H. Bream, R. E. Curiel, C.-R. Yu, C. E. Egwuagu, M. J. Grusby, T. M. Aune, and H. A. Young
IL-4 synergistically enhances both IL-2- and IL-12-induced IFN-{gamma} expression in murine NK cells
Blood, July 1, 2003; 102(1): 207 - 214.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
E. M. Schneider, I. Lorenz, M. Muller-Rosenberger, G. Steinbach, M. Kron, and G. E. Janka-Schaub
Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell-induced apoptosis
Blood, September 26, 2002; 100(8): 2891 - 2898.
[Abstract] [Full Text] [PDF]

Home page
 Arch DermatolHome page
O. Correia, L. Delgado, J.-C. Roujeau, L. Le Cleach, and J. A. Fleming-Torrinha
Soluble Interleukin 2 Receptor and Interleukin 1{alpha} in Toxic Epidermal Necrolysis: A Comparative Analysis of Serum and Blister Fluid Samples
Arch Dermatol, January 1, 2002; 138(1): 29 - 32.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. S. Chuang, P. R. Kumaresan, and P. A. Mathew
2B4 (CD244)-Mediated Activation of Cytotoxicity and IFN-{gamma} Release in Human NK Cells Involves Distinct Pathways
J. Immunol., December 1, 2001; 167(11): 6210 - 6216.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Rajagopalan, J. Fu, and E. O. Long
Cutting Edge: Induction of IFN-{gamma} Production but Not Cytotoxicity by the Killer Cell Ig-Like Receptor KIR2DL4 (CD158d) in Resting NK Cells
J. Immunol., August 15, 2001; 167(4): 1877 - 1881.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.