SKK4, A NOVEL ACTIVATOR OF STRESS-ACTIVATED PROTEIN KINASE-1 (SAPK1 JNK)/

A cDNA was cloned and expressed that encodes human stress-activated pr otein kinase kinase-4 (SKK4), a novel MAP kinase kinase family member whose mRNA is widely expressed in human tissues. SKK4 activated SAPK1/ JNK in vitro, but not SAPK2a/p38, SAPK2b/p38 beta, SAPK3/ERK6 or SAPK4 , It appears to be the mammalian homologue of HEP, an activator of SAP K1/JNK in Drosophila. In human epithelial KB cells SKK4 and SKK1/MKK4 (another activator of SAPK1/JNK) were both activated by stressful stim uli, but only SKK4 was activated by proinflammatory cytokines, The ide ntification of SKK4 explains why the major SAPK1/JNK activator detecte d in many mammalian cell extracts is chromatographically separable fro m SKK1/MKK4. (C) 1997 Federation of European Biochemical Societies.