Analysis of a novel regulator in JNK cascade and the application for apoptosis

Abstract

The mitogen-activated protein kinase (MAPK) cascades, in which the components are MAPK, MAPKK, MAPKKK, are conserved in eukaryotic signaling pathways. The general function of the MAPK cascades is to link a variety of extracellular stimuli to nuclear responses, i.e., the modulation of gene expression. In mammals, at least three MAPK cascades have been identified. The MAPKs in each pathway are JNK, p38, or ERK. Especially, JNK cascades are known to regulate stress responses and apoptosis. We successfully identified a novel serine-threonine kinase (STK) binding to MAPKKK such as MEKK1, MEKK2, or TAK1 in JNK cascade. The roles and substrates of the STK in cells are unknown. Overexpression of the STK inhibits the activation of MEKK1 or MEKK2. Then, we constructed the sh RNA expression vector for the STK and introduced into HELA cells. Knock-down of the STK led to the enhancement of MAPKKK activity and of stress-induced apoptosis.