Interleukin-2 induces γ-S-adenosyl-l-methionine synthetase gene expression during T-lymphocyte activation

The regulation of expression of the γ-S-adenosyl-L-methionine (AdoMet) synthetase gene was investigated in T-cells during G₀/G₁ transition, as well as throughout the G₁ phase. Stimulation of G₀ T-lymphocytes with concanavalin A induces AdoMet synthetase gene expression, starting 8 h after stimulation. Interleukin-2 (IL-2) stimulates the induction of this gene expression and AdoMet synthetase activity in G₁ lymphoblasts, in part by an increase in the transcription rate of the gene. Phorbol esters, which also stimulate the proliferation of G₁ lymphoblasts, show a similar kinetics of AdoMet synthetase mRNA induction. In contrast, the mRNA levels of the S-adenosyl-L-homocysteine hydrolase, another enzyme of the methionine cycle, remain unchanged upon IL-2 or phorbol 12,13-dibutyrate treatment. Dexamethasone and 8Br-cAMP, both inhibitors of lymphocyte proliferation, are able to block the expression of the AdoMet synthetase gene and, consequently, AdoMet synthetase activity. Together these findings indicate that the AdoMet synthetase gene is subject to cell-cycle regulation in T-lymphocytes