Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adult
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Amino Acid Sequence
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Animals
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Binding Sites
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Brain / enzymology
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Cell Cycle
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Cell Line
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Discs Large Homolog 1 Protein
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Drosophila / enzymology
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Female
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Guanylate Kinases
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HeLa Cells
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Humans
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Membrane Proteins
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Mice
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Mitogen-Activated Protein Kinase Kinases
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Molecular Sequence Data
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Placenta / enzymology
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Pregnancy
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Proteins / chemistry
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Proteins / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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Spodoptera
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Transfection
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Zebrafish
Substances
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Adaptor Proteins, Signal Transducing
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DLG1 protein, human
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Discs Large Homolog 1 Protein
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Dlg1 protein, mouse
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Membrane Proteins
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Proteins
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Recombinant Proteins
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Protein Serine-Threonine Kinases
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Mitogen-Activated Protein Kinase Kinases
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PDZ-binding kinase
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Guanylate Kinases