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XB-ART-47133
Mol Cell Proteomics September 1, 2013; 12 (9): 2587-603.

The human PDZome: a gateway to PSD95-Disc large-zonula occludens (PDZ)-mediated functions.

Belotti E , Polanowska J , Daulat AM , Audebert S , Thomé V , Lissitzky JC , Lembo F , Blibek K , Omi S , Lenfant N , Gangar A , Montcouquiol M , Santoni MJ , Sebbagh M , Aurrand-Lions M , Angers S , Kodjabachian L , Reboul J , Borg JP .


Abstract
Protein-protein interactions organize the localization, clustering, signal transduction, and degradation of cellular proteins and are therefore implicated in numerous biological functions. These interactions are mediated by specialized domains able to bind to modified or unmodified peptides present in binding partners. Among the most broadly distributed protein interaction domains, PSD95-disc large-zonula occludens (PDZ) domains are usually able to bind carboxy-terminal sequences of their partners. In an effort to accelerate the discovery of PDZ domain interactions, we have constructed an array displaying 96% of the human PDZ domains that is amenable to rapid two-hybrid screens in yeast. We have demonstrated that this array can efficiently identify interactions using carboxy-terminal sequences of PDZ domain binders such as the E6 oncoviral protein and protein kinases (PDGFRβ, BRSK2, PCTK1, ACVR2B, and HER4); this has been validated via mass spectrometry analysis. Taking advantage of this array, we show that PDZ domains of Scrib and SNX27 bind to the carboxy-terminal region of the planar cell polarity receptor Vangl2. We also have demonstrated the requirement of Scrib for the promigratory function of Vangl2 and described the morphogenetic function of SNX27 in the early Xenopus embryo. The resource presented here is thus adapted for the screen of PDZ interactors and, furthermore, should facilitate the understanding of PDZ-mediated functions.

PubMed ID: 23722234
PMC ID: PMC3769332
Article link: Mol Cell Proteomics

Genes referenced: actl6a acvr2b brsk2 calr cdk16 dlg4 fn1 hrg myc scrib snx27 sox2 vangl2
Morpholinos: snx27 MO1 vangl2 MO1


Article Images: [+] show captions
References [+] :
Anastas, A protein complex of SCRIB, NOS1AP and VANGL1 regulates cell polarity and migration, and is associated with breast cancer progression. 2012, Pubmed


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