JNK, but not MAPK, activation is associated with Fas-mediated apoptosis in human T cells.
Fas is a cell surface molecule that is expressed on a wide array of cell types and triggers apoptosis. While in most situations Fas ligation activates programmed cell death, on resting T lymphocytes it can co-stimulate proliferation with the T cell receptor (TCR)/CD3 complex. This incongruity suggests that Fas may elicit signaling events that overlap with those used by proliferation cues. We observe that in the human T cell line Jurkat and in human peripheral blood lymphocytes, Fas stimulation does not signal by the Ras/Raf-1/mitogen-activated protein kinase (MAPK) pathway or by increased intracellular calcium. Rather, Fas ligation strongly activates Jun kinase (JNK). This activity, as well as Fas-induced apoptosis, is blocked by increased levels of cAMP. The balance between proliferation and apoptosis by Fas triggering of T lymphocytes may therefore reflect a signaling ratio between TCR activation of the Ras/Raf-1/MAPK pathway versus JNK activation by Fas.
Wilson
D J
DJ
Department of Medicine, University of Vermont, Burlington 05405, USA.
Fortner
K A
KA
Lynch
D H
DH
Mattingly
R R
RR
Macara
I G
IG
Posada
J A
JA
Budd
R C
RC
D017209:Apoptosis / Q000276:immunology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis*; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation; D008223:Lymphoma; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D011494:Protein Kinases / Q000096:biosynthesis*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D007376:Interleukin-2; D019014:fas Receptor; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases