Details

Autor(en) / Beteiligte

• 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

Titel

Rewiring of RSK–PDZ Interactome by Linear Motif Phosphorylation

Ist Teil von

• Journal of molecular biology, 2019-03, Vol.431 (6), p.1234-1249

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •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.