Differential regulation of methionine adenosyltransferase in superantigen and mitogen stimulated human T lymphocytes

被引:37
|
作者
LeGros, HL
Geller, AM
Kotb, M
机构
[1] UNIV TENNESSEE,CTR HLTH SCI,DEPT BIOCHEM,MEMPHIS,TN 38163
[2] UNIV TENNESSEE,CTR HLTH SCI,DEPT MICROBIOL & IMMUNOL,MEMPHIS,TN 38163
[3] UNIV TENNESSEE,CTR HLTH SCI,DEPT SURG,MEMPHIS,TN 38163
[4] VET ADM MED CTR,MEMPHIS,TN 38104
关键词
D O I
10.1074/jbc.272.25.16040
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Superantigens interact with the T tell 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 (SEE) 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 SEE, MAT II activity was comparable in both cultures. Both stimuli caused down-regulation of the MAT 68-kDa lambda subunit expression and induced a comparable increase in the expression of the catalytic alpha 2/alpha 2' subunit mRNA and protein. However, in superantigen-stimulated cells, the expression of the noncatalytic beta 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 alpha 2/alpha 2' and beta subunits while SEB-stimulated cells expressed the alpha 2/alpha 2' subunits only; the beta subunit was no longer expressed in superantigen-stimulated cells. Kinetic analysis of MAT II in extracts of PHA- and SEE-stimulated cells using reciprocal kinetic plots revealed that in the absence of the beta subunit the K-m of the enzyme for L-methionine (L-Met) was S-fold higher than in the presence of the beta subunit. Furthermore, AdoMet levels were 5-fold higher in cell extracts lacking the beta subunit (SEB-stimulated cell extracts) compared with extracts containing MAT II alpha 2/alpha 2' and beta subunits. We propose that the increased levels of AdoMet in superantigen-stimulated cells may be attributed to the absence of the beta subunit, which seems to have rendered MAT II less sensitive to product feedback inhibition by (-)AdoMet. The data suggest that the beta 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 beta 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.
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页码:16040 / 16047
页数:8
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