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Role of mitogen‐activated protein kinases in activation‐induced apoptosis of T cells
Author(s) -
Li Zhu,
Xue-Zhong Yu,
Yoshiki Akatsuka,
Jonathan A. Cooper,
Claudio Anasetti
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00756.x
Subject(s) - mapk/erk pathway , fas ligand , apoptosis , kinase , microbiology and biotechnology , mitogen activated protein kinase , protein kinase a , ask1 , fas receptor , signal transduction , biology , programmed cell death , chemistry , cancer research , mitogen activated protein kinase kinase , biochemistry
A member of the mitogen‐activated protein (MAP) kinase family, Jun N‐terminal kinase (JNK), has been implicated in regulating apoptosis in various cell types. We have investigated the requirement for another type of MAP kinase, extracellular signal‐regulated protein kinase (ERK) in activation‐induced cell death (AICD) of T cells. AICD is the process by which recently activated T cells undergo apoptosis when restimulated through the T‐cell antigen receptor. Here we show that both JNK and ERK are activated rapidly upon T‐cell receptor (TCR) ligation prior to the onset of AICD. A chemical inhibitor of ERK activation, PD 098059, inhibits ERK activation and apoptosis, while JNK activation is not inhibited. This suggests that JNK activation is not sufficient for apoptosis. TCR cross‐linking induces expression of the apoptosis‐inducing factor, Fas ligand (FasL), and its expression correlates with ERK activation. In addition, apoptosis induced by direct ligation of the Fas receptor by anti‐Fas antibody is not associated with ERK activation and is not inhibited by PD 098059. These data suggest that ERK activation is an early event during T‐cell apoptosis induced by antigen–receptor ligation, and is not involved in apoptosis per se but in the expression of FasL. MAP kinase family members may be similarly involved in inducing apoptosis signals in other cell types.