| Summary: | 碩士 === 中山醫學院 === 口腔醫學研究所 === 89 === Abstract
The protein kinase of mixed-lineage kinase (MLK) was recently identified. The kinase domain of MLK family proteins belongs to MAPKKK of MAPK cascade, which is followed by one or two leucine zipper domains and specifically activate JNK/SAPK. A novel protein kinase ZAK was published by Liu et al. lately. Due to its possessing of a domain with structure and function similar to that of kinase domain and characteristic of containing leucine zipper, it was classified as a new member of MLK family. In addition to JNK/SAPK, ZAK also activates NF-κB. Moreover it has been proven that ZAK induces cytotoxicity of Hep3B hepatoma cell line via apoptosis.
This study was aimed at mapping the apoptotic domain of ZAK by analyzing ZAK proteins which are a series of sequential deletions strating from C terminals. Surprisingly, when the portion of ZAK from C terminal to SAM domain were largely deleted but it still retains partial SAM domain, it no longer activates JNK/SAPK and decreases its cytotoxicity noticeablely. And the mutated ZAKs were observed in both cytoplasms and nuclei, albeit it was only found in cytoplasms originally. Mutated ZAKs regain its capability to activate JNK/SAPK while remain to be located in nuclei and have a decreasing cytotoxicity until the SAM domain was completely removed. These results suggested that SAM domain of ZAK might be responsible for or artibute to localization and this might be a mechanism for how ZAK induce apoptosis of Hep3B cell line.
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