ACTIVATION OF BCL-2 SUPPRESSIBLE 40 AND 44 KDA P38-LIKE KINASES DURING APOPTOSIS OF EARLY AND LATE B LYMPHOCYTIC CELL-LINES

Activation of several different kinases characterizes the induction of apoptosis, Abelson virus transformed pre-B lymphocytes undergo apopto sis within 24 h of serum deprivation, PKA activation or gamma-irradiat ion, and the activity of two kinases of ca, 40 and 44 kDa is specifica lly induced during this apoptotic process. Bcl-2 expression prevents b oth apoptosis and the induction of these kinases, Immunologic and subs trate similarities indicate that these kinases are related to the p38 family of MAP kinases, More mature cells of the B lymphocytic lineage, plasmacytomas, also exhibit induction of these kinases when apoptosis is induced by withdrawal of serum or IL-6, Treatment of the pre-B cel ls with ICE protease inhibitors when apoptotic stimuli are delivered p revents induction of the kinase activity, and partially inhibits apopt osis, These findings indicate that the induction of these 40 and 44 kD a p38 related kinases is a common feature of apoptosis in mouse B lymp hocytic cells and may represent a step downstream of ICE proteases in the signal cascade that leads to programmed cell death. (C) 1998 Feder ation of European Biochemical Societies.