Rewiring of RSK-PDZ Interactome by Linear Motif Phosphorylation.

Fiche publication


Date publication

février 2019

Journal

Journal of molecular biology

Auteurs

Membres identifiés du Cancéropôle Est :
Dr TRAVE Gilles, Dr NOMINE Yves, Dr GOGL Gergo


Tous les auteurs :
Gógl G, Biri-Kovács B, Durbesson F, Jane P, Nomine Y, Kostmann C, Bilics V, Simon M, Reményi A, Vincentelli R, Trave G, Nyitray L

Résumé

Phosphorylation of short linear peptide motifs is a widespread process for the dynamic regulation of protein-protein interactions. However, the global impact of phosphorylation events on the protein-protein interactome is rarely addressed. The disordered C-terminal tail of ribosomal S6 kinase 1 (RSK1) binds to PDZ domain-containing scaffold proteins, and it harbors a phosphorylatable PDZ binding motif (PBM) responsive to epidermal growth factor (EGF) stimulation. Here, we examined binding of two versions of the RSK1 PBM, either phosphorylated or unphosphorylated at position -3, to almost all (95%) of the 266 PDZ domains of the human proteome. PBM phosphorylation dramatically altered the PDZ domain-binding landscape of RSK1, by strengthening or weakening numerous interactions to various degrees. The RSK-PDZome interactome analyzed in this study reveals how linear motif-based phospho-switches convey stimulus-dependent changes in the context of related network components.

Mots clés

MAPK, PDZ, RSK, phosphorylation, protein–protein interaction

Référence

J. Mol. Biol.. 2019 Feb 3;: