Rewiring of RSK-PDZ Interactome by Linear Motif Phosphorylation

Gógl, Gergő and Biri-Kovács, Beáta and Durbesson, Fabien and Jane, Pau and Nomine, Yves and Kostmann, Camille and Bilics, Viktória and Simon, Márton and Reményi, Attila and Vincentelli, Renaud and Trave, Gilles and Nyitray, László (2019) Rewiring of RSK-PDZ Interactome by Linear Motif Phosphorylation. JOURNAL OF MOLECULAR BIOLOGY. ISSN 0022-2836 (In Press)

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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 (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.

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