EXTRACELLULAR SIGNAL-REGULATED KINASE-2, BUT NOT C-JUN NH2-TERMINAL KINASE, ACTIVATION CORRELATES WITH SURFACE IGM-MEDIATED APOPTOSIS IN THE WEHI-231 B-CELL LINE

Both extracellular signal-regulated kinase (ERK) and c-Jun NH2-termina l kinase (JNK) have been implicated in mediating the signaling events that precede apoptosis. We studied the activation of these kinases dur ing apoptosis of WEHI 231 B cells, Surface IgM ligation induces apopto sis of WEHI 231 cells. This effect is augmented by simultaneous engage ment of CD95 and is inhibited by costimulation with either CD40 or IL- 4R, We determined that surface IgM ligation activates ERK2 to a much g reater level than JNK, and that IgM-mediated ERK2 activation is enhanc ed by costimulation with anti-CD95, Costimulation with either IL-4 or anti-CD40 interferes with anti-IgM-stimulated ERK2 activation. Transie nt expression of mitogen-activated protein kinase phosphatase-l (MKP-1 ) inhibits both ERK2 activation and cell death following stimulation w ith anti-IgM and the combination of anti-IgM plus anti-CD95, CD40 enga gement alone activates JNK, but IL-4 stimulation does not. N-acetyl-L- cysteine pretreatment, which blocks CD40-mediated JNK activation, does not affect the ability of CD40 to inhibit anti-IgM-mediated ERK2 acti vation and apoptosis, Together, these data suggest that JNK activation is not required for CD40 inhibition of surface IgM-induced cell death and that ERK2 plays an active role in mediating anti-IgM-induced apop tosis of WEHI 231 B cells.