A ROLE FOR JNK SAPK IN PROLIFERATION, BUT NOT APOPTOSIS, OF IL-3-DEPENDENT CELLS/

Activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) has been implicated in the induction of apoptosis in a vari ety of systems [1-8]. BAF3 cells are pre-B cells that undergo apoptosi s following IL-3 withdrawal or ceramide treatment [9,10], JNK/SAPK in BAF3 cells is stimulated by ceramide and also during cell proliferatio n in response to IL-3 [11], but its role in the apoptotic response is not clear, We have devised a method of selectively inhibiting JNK/SAPK activity using a dual-specificity threonine/tyrosine phosphatase, M3/ 6. Expression of this phosphatase in BAF3 cells prevented ceramide sti mulation of JNK/SAPK activity but did not affect apoptosis following I L-3 withdrawal or ceramide treatment, IL-3-stimulated proliferation of BAF3 cells expressing the phosphatase was, however, inhibited, Hence JNK/SAPK activation is likely to be involved in the proliferative resp onse of these cells but is not required for apoptosis. Selective ablat ion by dual-specificity phosphatases should be a general method for de termining the functions of specific mitogen-activated kinase pathways.