Rewiring of RSK–PDZ Interactome by Linear Motif Phosphorylation. Issue 6 (15th March 2019)

• Record Type: Journal Article
• Authors: Gógl, Gergő; Biri-Kovács, Beáta; Durbesson, Fabien; Jane, Pau; Nomine, Yves; Kostmann, Camille; Bilics, Viktória; Simon, Márton; Reményi, Attila; Vincentelli, Renaud; Trave, Gilles; Nyitray, László
• Is Part Of: Journal of molecular biology. Volume 431:Issue 6(2019)
• Page Start: 1234
• Page End: 1249
• Publication Date: 2019-03-15
• Subjects: phosphorylation -- PDZ -- RSK -- MAPK -- protein–protein interaction; PBMs PDZ-binding motifs -- RSK ribosomal S6 kinase -- BIs binding intensities -- ITC isothermal titration calorimetry -- SPR surface plasmon resonance -- FP fluorescence polarization -- WT wild type; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2019.01.038
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: 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 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. Graphical Abstract: Unlabelled Image Highlights: RSK–PDZ interactions are regulated by phosphorylation. RSK can recognize at least 34 PDZ domains in the human proteome. PDZ-mediated interactions are crucial in substrate targeting. Growth factor-induced RSK phosphorylation modulates the affinity of these interactions.