p38 mitogen-activated protein kinase is involved in Fas ligand expression.
p38 mitogen-activated protein kinase (MAPK) is activated by T cell receptor engagement. Here we showed that T cell receptor activated p38alpha but not p38delta. Inhibition of p38alpha by the specific inhibitor SB 203580 prevented activation-induced cell death in T cells. SB 203580 had no effect on Fas-initiated apoptosis. Instead, SB 203580 preferentially inhibited activation-induced Fas ligand (FasL) expression. The inhibition on FasL expression by SB 203580 was correlated with the suppression on the FasL promoter activation. Overexpression of active MAPK kinase 3b, the activator of p38 MAPK, led to activation of FasL promoter and induction of FasL transcripts in T cells. Stress stimulation of T cells by anisomycin also induced FasL expression in a p38 MAPK-dependent manner. The induction of FasL expression in nonlymphoid cells such as 293T also required activation of p38 MAPK. Our results suggest that p38 MAPK is essential for FasL expression.
Hsu
S C
SC
Graduate Institute of Microbiology, National Taiwan University School of Medicine, Taipei 10018, Taiwan, R.O.C.
Gavrilin
M A
MA
Tsai
M H
MH
Han
J
J
Lai
M Z
MZ
D017209:Apoptosis / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases