Characterization of PDZ-binding kinase, a mitotic kinase.
hDlg, the human homologue of the Drosophila Discs-large (Dlg) tumor suppressor protein, is known to interact with the tumor suppressor protein APC and the human papillomavirus E6 transforming 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 hDlg through its C-terminal T/SXV motif. PBK and hDlg are phosphorylated at mitosis in HeLa cells, and the mitotic phosphorylation 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 transduction pathways regulating the cell cycle or cellular proliferation.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adult, Amino Acid Sequence, Animals, Binding Sites, Brain, Cell Cycle, Cell Line, Discs Large Homolog 1 Protein, Drosophila, Female, Guanylate Kinases, HeLa Cells, Humans, Membrane Proteins, Mice, Mitogen-Activated Protein Kinase Kinases, Molecular Sequence Data, Placenta, Pregnancy, Protein Serine-Threonine Kinases, Proteins, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Spodoptera, Transfection, Zebrafish
Adaptor Proteins, Signal Transducing, Adult, Amino Acid Sequence, Animals, Binding Sites, Brain, Cell Cycle, Cell Line, Discs Large Homolog 1 Protein, Drosophila, Female, Guanylate Kinases, HeLa Cells, Humans, Membrane Proteins, Mice, Mitogen-Activated Protein Kinase Kinases, Molecular Sequence Data, Placenta, Pregnancy, Protein Serine-Threonine Kinases, Proteins, Recombinant Proteins, Sequence Alignment, Sequence Homology, Amino Acid, Spodoptera, Transfection, Zebrafish
Proc Natl Acad Sci U S A
Date: May. 09, 2000
PubMed ID: 10779557
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