Characterization of PDZ-binding kinase, a mitotic kinase

Proc Natl Acad Sci U S A. 2000 May 9;97(10):5167-72. doi: 10.1073/pnas.090102397.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Brain / enzymology
  • Cell Cycle
  • Cell Line
  • Discs Large Homolog 1 Protein
  • Drosophila / enzymology
  • Female
  • Guanylate Kinases
  • HeLa Cells
  • Humans
  • Membrane Proteins
  • Mice
  • Mitogen-Activated Protein Kinase Kinases
  • Molecular Sequence Data
  • Placenta / enzymology
  • Pregnancy
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteins / chemistry
  • Proteins / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Spodoptera
  • Transfection
  • Zebrafish

Substances

  • Adaptor Proteins, Signal Transducing
  • DLG1 protein, human
  • Discs Large Homolog 1 Protein
  • Dlg1 protein, mouse
  • Membrane Proteins
  • Proteins
  • Recombinant Proteins
  • Protein Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • PDZ-binding kinase
  • Guanylate Kinases

Associated data

  • GENBANK/AF189722