Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif

A novel mixed lineage kinase-like protein ZAK, containing a leucine-zipper (LZ) and a sterile-alpha motif (SAM), was cloned. This cDNA has 2456 bp and encodes a protein of 800 amino acids that contains a kinase catalytic doma in, a leucine-zipper and a SAM. The molecular weight of this protein is 91k Da. Northern blot analysis revealed that the expression of this ZAK gene is found in various parts of human tissues. We also found that ZAK proteins m ight form homodimers or oligomers in mammalian cells. MLKs have been propos ed to function as mitogen-activated protein kinase kinase kinase in pathway s leading to MAPK cascade. The expression of ZAK in mammalian cells specifi cally leads to the activation of the JNK/SAPK pathway as well as the activa tion of transcription factor, NF-kappa B. Overexpression of the ZAK gene in duces the apoptosis of a hepatoma cell line, (C) 2000 Academic Press.