Activation of T cells by superantigen: cytokine production but not apoptosis depends on MEK-1 activity.
Engagement of the TCR may result in proliferation and cytokine release or programmed cell death. These two outcomes may be the consequence of distinct T cell receptor-coupled signal transduction pathways or may reflect quantitative differences in signaling strength via a single pathway. Here we show that genetic inhibition of MAP kinase kinase (MEK) by a dominant negative mutant or through chemical inhibition by PD98059 inhibits IL-2 secretion but not programmed cell death after TCR ligation by superantigen. This supports the hypothesis that T cell cytokine release and apoptosis result from signaling through distinct pathways and implies that the molecular signaling mechanisms regulating apoptosis of mature T cells and negative selection of thymocytes may be similar.
Adler
B
B
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Weber
G F
GF
Cantor
H
H
D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000096:biosynthesis*; D005419:Flavonoids / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D048369:MAP Kinase Kinase 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D020929:Mitogen-Activated Protein Kinase Kinases; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D005419:Flavonoids; D007376:Interleukin-2; D018089:Superantigens; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one