Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl

Jinwei Zhu, Yuan Shang, Qingwen Wan, Yitian Xia, Jia Chen, Quansheng Du, Mingjie Zhang

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The tumor suppressors Discs Large (Dlg), Lethal giant larvae (Lgl) and Scribble are essential for the establishment and maintenance of epithelial cell polarity in metazoan. Dlg, Lgl and Scribble are known to interact strongly with each other genetically and form the evolutionarily conserved Scribble complex. Despite more than a decade of extensive research, it has not been demonstrated whether Dlg, Lgl and Scribble physically interact with each other. Here, we show that Dlg directly interacts with Lgl in a phosphorylation-dependent manner. Phosphorylation of any one of the three conserved Ser residues situated in the central linker region of Lgl is sufficient for its binding to the Dlg guanylate kinase (GK) domain. The crystal structures of the Dlg4 GK domain in complex with two phosphor-Lgl2 peptides reveal the molecular mechanism underlying the specific and phosphorylation-dependent Dlg/Lgl complex formation. In addition to providing a mechanistic basis underlying the regulated formation of the Scribble complex, the structure of the Dlg/Lgl complex may also serve as a starting point for designing specific Dlg inhibitors for targeting the Scribble complex formation.

Original languageEnglish (US)
Pages (from-to)451-463
Number of pages13
JournalCell Research
Volume24
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Dlg
  • Lgl
  • cell polarity
  • crystal structure
  • phosphorylation-dependent interaction
  • tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Zhu, J., Shang, Y., Wan, Q., Xia, Y., Chen, J., Du, Q., & Zhang, M. (2014). Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl. Cell Research, 24(4), 451-463. https://doi.org/10.1038/cr.2014.16