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) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by LeGros Jr., H L. Articles by Kotb, M. Search for Related Content PubMed PubMed Citation Articles by LeGros Jr., H L. Articles by Kotb, M. Social Bookmarking                      What's this?

Volume 272, Number 25, Issue of June 20, 1997 pp. 16040-16047
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Differential Regulation of Methionine Adenosyltransferase in Superantigen and Mitogen Stimulated Human T Lymphocytes

(Received for publication, November 20, 1996, and in revised form, April 16, 1997)

H Leighton LeGros Jr.^§ , Arthur M. Geller ^¶ and Malak Kotb ^§

From the Departments of  Surgery, ^¶ Biochemistry, and  Microbiology and Immunology, The University of Tennessee, Memphis, Tennessee, 38163 and ^§ The Veterans Administration Medical Center, Memphis, Tennessee 38104

Superantigens interact with the T cell receptor for antigen (TCR) and are, therefore, more physiological stimulators of T lymphocytes than nonspecific polyclonal T cell mitogens. The effects of these two classes of T cell stimulators on methionine adenosyltransferase (MAT) and S-adenosylmethionine (AdoMet) levels were investigated. Activation of resting human peripheral blood T lymphocytes by the mitogen phytohemagglutinin (PHA) or the superantigen staphylococcal enterotoxin B (SEB) caused a 3- to 6-fold increase in MAT II specific activity. Although the proliferative response was higher in cultures stimulated with PHA compared with SEB, MAT II activity was comparable in both cultures. Both stimuli caused down-regulation of the MAT 68-kDa  subunit expression and induced a comparable increase in the expression of the catalytic 2/2 subunit mRNA and protein. However, in superantigen-stimulated cells, the expression of the noncatalytic  subunit was down-regulated and virtually disappeared by 72 h post-stimulation; whereas, no change in the expression of this subunit was noted in PHA-stimulated cells. Thus, at 72 h following stimulation, PHA-stimulated cells expressed MAT II 2/2 and  subunits while SEB-stimulated cells expressed the 2/2 subunits only; the  subunit was no longer expressed in superantigen-stimulated cells. Kinetic analysis of MAT II in extracts of PHA- and SEB-stimulated cells using reciprocal kinetic plots revealed that in the absence of the  subunit the K_m of the enzyme for L-methionine (L-Met) was 3-fold higher than in the presence of the  subunit. Furthermore, AdoMet levels were 5-fold higher in cell extracts lacking the  subunit (SEB-stimulated cell extracts) compared with extracts containing MAT II 2/2 and  subunits. We propose that the increased levels of AdoMet in superantigen-stimulated cells may be attributed to the absence of the  subunit, which seems to have rendered MAT II less sensitive to product feedback inhibition by ()AdoMet. The data suggest that the  subunit of MAT II, which has no catalytic activity, may be a regulatory subunit that imparts a lower K_m for L-Met but increases the sensitivity to feedback inhibition by AdoMet. The down-regulation of the  subunit, which occurred when T cells were stimulated via the TCR, may be an important mechanism to regulate AdoMet levels at different stages of T cell differentiation under physiological conditions.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. R. Attia, L. A. Gardner, E. Mahrous, D. J. Taxman, L. LeGros, S. Rowe, J. P.-Y. Ting, A. Geller, and M. Kotb Selective Targeting of Leukemic Cell Growth in Vivo and in Vitro Using a Gene Silencing Approach to Diminish S-Adenosylmethionine Synthesis J. Biol. Chem., November 7, 2008; 283(45): 30788 - 30795. [Abstract] [Full Text] [PDF]

				J. M. MATO, F. J. CORRALES, S. C. LU, and M. A. AVILA S-Adenosylmethionine: a control switch that regulates liver function FASEB J, January 1, 2002; 16(1): 15 - 26. [Abstract] [Full Text] [PDF]

				H. L. LeGros Jr., A.-B. Halim, A. M. Geller, and M. Kotb Cloning, Expression, and Functional Characterization of the beta Regulatory Subunit of Human Methionine Adenosyltransferase (MAT II) J. Biol. Chem., January 28, 2000; 275(4): 2359 - 2366. [Abstract] [Full Text] [PDF]

				A.-B. Halim, L. LeGros, A. Geller, and M. Kotb Expression and Functional Interaction of the Catalytic and Regulatory Subunits of Human Methionine Adenosyltransferase in Mammalian Cells J. Biol. Chem., October 15, 1999; 274(42): 29720 - 29725. [Abstract] [Full Text] [PDF]

				R. S. Dwivedi, L.-J. Wang, and B. L. Mirkin S-Adenosylmethionine Synthetase Is Overexpressed in Murine Neuroblastoma Cells Resistant to Nucleoside Analogue Inhibitors of S-Adenosylhomocysteine Hydrolase: A Novel Mechanism of Drug Resistance Cancer Res., April 1, 1999; 59(8): 1852 - 1856. [Abstract] [Full Text] [PDF]

				A.-B. Halim, L. LeGros, M. E. Chamberlin, A. Geller, and M. Kotb Regulation of the Human MAT2A Gene Encoding the Catalytic alpha 2 Subunit of Methionine Adenosyltransferase, MAT II. GENE ORGANIZATION, PROMOTER CHARACTERIZATION, AND IDENTIFICATION OF A SITE IN THE PROXIMAL PROMOTER THAT IS ESSENTIAL FOR ITS ACTIVITY J. Biol. Chem., March 23, 2001; 276(13): 9784 - 9791. [Abstract] [Full Text] [PDF]

				L. LeGros, A.-B. Halim, M. E. Chamberlin, A. Geller, and M. Kotb Regulation of the Human MAT2B Gene Encoding the Regulatory beta Subunit of Methionine Adenosyltransferase, MAT II J. Biol. Chem., June 29, 2001; 276(27): 24918 - 24924. [Abstract] [Full Text] [PDF]