Characterization of PDZ-binding kinase, a mitotic kinase

摘要

hDlg, the human homologue of the Drosophila Discs-large (DIg) tumor suppressor protein. is known to interact with the tumor suppressor protein APC and the human papillomavirus E6 trans- forming protein. In a two-hybrid screen, we identified a 322-aa serine/threonine kinase that binds to the PDZ2 domain of hDlg. The mRNA for this PDZ-binding kinase. or PBK. is most abundant in placenta and absent from adult brain tissue. The protein sequence of PBK has all the characteristic protein kinase subdomains and a C-terminal PDZ-binding T/SXV motif. In vitro. PBK binds specifically to PDZ2 of hDIg through its C-terminal T/SXV motif. PBK and hDlg are phosphorylated at mitosis in HeLa cells, and the mitotic phos- phorylation of PBK is required for its kinase activity. In vitro. cdc2/cyclin B phosphorylates PBK. This evidence shows how PBK could link hDlg or other PDZ-containing proteins to signal trans- duction pathways regulating the cell cycle or cellular proliferation.