HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, Y. Q. Articles by Ferrante, A. Search for Related Content PubMed PubMed Citation Articles by Li, Y. Q. Articles by Ferrante, A.

Regulation of Lymphotoxin Production by the p21^ras-raf-MEK-ERK Cascade in PHA/PMA-Stimulated Jurkat Cells¹

Yong Q. Li^*, Charles S. T. Hii^2,*, Maurizio Costabile^*, David Goh^*, Channing J. Der and Antonio Ferrante^*

^* Department of Immunopathology, Women’s and Children’s Hospital, North Adelaide, Australia; and Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599

Although the production of lymphotoxin (LT) from activated Th1 lymphocytes has been reported extensively, the intracellular signaling mechanisms that regulate this T cell function remain totally undefined. We have examined whether the p21^ras-raf-1-mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) kinase (MEK)-ERK cascade plays a role in regulating the production of LT, because the activity of these signaling molecules is up-regulated in activated T lymphocytes. Transfection of Jurkat leukemic T cells with a dominant negative mutant of p21^ras (ras17N or ras15A), raf-1 (raf 1–130), or ERK1 (Erk1-K71R) resulted in the suppression of the mitogen/phorbol ester-stimulated production/secretion of LT. This suppression was accompanied by a parallel inhibition of mitogen-stimulated ERK activation. The selective antagonist of MEK1 activation, PD98059, also attenuated the mitogen-stimulated or anti-CD3 Ab and phorbol ester-stimulated production of LT from Jurkat cells or peripheral blood T lymphocytes. This study provides, for the first time, direct evidence that the p21^ras-raf-MEK-ERK cascade plays a vital role in regulating the production of LT.

This article has been cited by other articles:

				Y.-N. Zhu, W.-M. Zhao, Y.-F. Yang, Q.-F. Liu, Y. Zhou, J. Tian, J. Ni, Y.-F. Fu, X.-G. Zhong, W. Tang, et al. Periplocoside E, an Effective Compound from Periploca sepium Bge, Inhibited T Cell Activation in Vitro and in Vivo J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 662 - 669. [Abstract] [Full Text] [PDF]

				M. Costabile, C. S. T. Hii, M. Melino, C. Easton, and A. Ferrante The Immunomodulatory Effects of Novel {beta}-Oxa, {beta}-Thia, and {gamma}-Thia Polyunsaturated Fatty Acids on Human T Lymphocyte Proliferation, Cytokine Production, and Activation of Protein Kinase C and MAPKs J. Immunol., January 1, 2005; 174(1): 233 - 243. [Abstract] [Full Text] [PDF]

				Y. Takagi, J. Du, X.-Y. Ma, I. Nakashima, and F. Nagase Phorbol 12-Myristate 13-Acetate Protects Jurkat Cells from Methylglyoxal-Induced Apoptosis by Preventing c-Jun N-Terminal Kinase-Mediated Leakage of Cytochrome c in an Extracellular Signal-Regulated Kinase-Dependent Manner Mol. Pharmacol., March 1, 2004; 65(3): 778 - 787. [Abstract] [Full Text] [PDF]

				H.-W. Lee, D.-H. Ahn, S. C. Crawley, J.-D. Li, J. R. Gum Jr., C. B. Basbaum, N. Q. Fan, D. E. Szymkowski, S.-Y. Han, B. H. Lee, et al. Phorbol 12-Myristate 13-Acetate Up-regulates the Transcription of MUC2 Intestinal Mucin via Ras, ERK, and NF-kappa B J. Biol. Chem., August 30, 2002; 277(36): 32624 - 32631. [Abstract] [Full Text] [PDF]

				M. Costabile, C. S. T. Hii, B. S. Robinson, D. A. Rathjen, M. Pitt, C. Easton, R. C. Miller, A. Poulos, A. W. Murray, and A. Ferrante A Novel Long Chain Polyunsaturated Fatty Acid, {beta}-Oxa 21:3n-3, Inhibits T Lymphocyte Proliferation, Cytokine Production, Delayed-Type Hypersensitivity, and Carrageenan-Induced Paw Reaction and Selectively Targets Intracellular Signals J. Immunol., October 1, 2001; 167(7): 3980 - 3987. [Abstract] [Full Text] [PDF]