Volume 24, No 4, Apr 2014
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 24 Issue 4, April 2014: 451-463
ORIGINAL ARTICLES
Phosphorylation-dependent interaction between tumor suppressors Dlg and Lgl
Jinwei Zhu1,*, Yuan Shang1,*, Qingwen Wan3, Yitian Xia1, Jia Chen1,4, Quansheng Du3 and Mingjie Zhang1,2
1Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
2Center of Systems Biology and Human Health, School of Science and Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
3Department of Neurology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA
4Current address: The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK
Correspondence: Mingjie Zhang,(mzhang@ust.hk)
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.
10.1038/cr.2014.16
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