MAPKKK6, a novel mitogen-activated protein kinase kinase kinase, that associates with MAPKKK5

MAPRKK5/ASK1 activates c-Jun N-terminal kinase (JNK) and p38 kinase signali ng pathways and induces apoptosis when expressed in stably transfected cell s. Using MAPKKK5 as bait in yeast two-hybrid screening, a novel protein tha t interacts with MAPKKK5 was identified and cloned. This novel protein is p redicted to contain all 11 kinase subdomains and shares 45% amino acid iden tity with MAPKKK5 and thus is designated MAPKKK6. The interaction of MAPKKK 6 with MAPKKK5 in vivo was confirmed by coexpression of MAPKKK5 and MAPKKK6 in 293 cells followed by immunoprecipitation. In contrast to MAPKKK5, whic h activated both JNK and p38 kinase pathways, MAPKKK6 only weakly activated JNK but not ERK or p38 kinase pathways. (C) 1998 Academic Press.