Journal
EMBO JOURNAL
Volume 30, Issue 24, Pages 4986-4997Publisher
WILEY
DOI: 10.1038/emboj.2011.428
Keywords
GKAP/SAPAP; LGN/Pins; MAGUK; scaffold proteins; SH3-GK domains
Categories
Funding
- National Major Basic Research Program [2009CB918600]
- National Science Foundation of China [30970574]
- Shanghai Rising-Star Program [10QA1400700]
- RGC [663808, 664009, 660709, 663610, HKUST6/CRF/10, SEG_HKUST06, AoE/B-15/01-II, AoE/M-04/04]
Ask authors/readers for more resources
Membrane-associated guanylate kinases (MAGUKs) are a large family of scaffold proteins that play essential roles in tissue developments, cell-cell communications, cell polarity control, and cellular signal transductions. Despite extensive studies over the past two decades, the functions of the signature guanylate kinase domain (GK) of MAGUKs are poorly understood. Here we show that the GK domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein LGN in a phosphorylation-dependent manner. The structure of the DLG1 SH3-GK tandem in complex with a phospho-LGN peptide reveals that the GMP-binding site of GK has evolved into a specific pSer/pThr-binding pocket. Residues both N- and C-terminal to the pSer are also critical for the specific binding of the phospho-LGN peptide to GK. We further demonstrate that the previously reported GK domain-mediated interactions of DLGs with other targets, such as GKAP/DLGAP1/SAPAP1 and SPAR, are also phosphorylation dependent. Finally, we provide evidence that other MAGUK GKs also function as phospho-peptide-binding modules. The discovery of the phosphorylation-dependent MAGUK GK/target interactions indicates that MAGUK scaffold-mediated signalling complex organizations are dynamically regulated. The EMBO Journal (2011) 30, 4986-4997. doi: 10.1038/emboj.2011.428; Published online 25 November 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available