Modulated kinase activities, in cells undergoing tumour necrosis, factor-induced apoptotic cell death

Tumour necrosis, factor-alpha (TNF) has, a variety of cellular effects incl uding apoptotic, and necrotic cytotoxicity. TNF activates a range of kinase s, but their role in cytotoxic mechanisms is unclear. HeLa cells expressing elevated type II 75 kDa TNF receptor (TNFR2) protein, analysed by flow cyt ometry and Western analysis, showed altered c-Jun N-terminal kinase (JNK) a nd p38 mitogen-activated protein kinase (p38MAPK; but not MAPK) protein con tent and activation. There was greater JNK activation, but reduced p38MAPK activation in dying cells compared to those still to enter TNF-induced apop tosis. Moreover, cells displaying more rapid apoptosis possess higher level s of type I 55 kDa TNFR1 receptor isoform, but less TNFR2. These findings r eveal differential kinase activation in TNF-induced apoptotic death. (C) 20 01 Federation of European Biochemical Societies. Published by Elsevier Scie nce B.V. All rights reserved.