RT Journal Article
SR Electronic
T1 Rewiring of RSK-PDZ interactions by linear motif phosphorylation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 419721
DO 10.1101/419721
A1 Gergo Gogl
A1 Beata Biri-Kovacs
A1 Fabien Durbesson
A1 Pau Jane
A1 Yves Nomine
A1 Camille Kostmann
A1 Viktoria Bilics
A1 Marton Simon
A1 Attila Remenyi
A1 Renaud Vincentelli
A1 Gilles Trave
A1 Laszlo Nyitray
YR 2018
UL http://biorxiv.org/content/early/2018/09/17/419721.abstract
AB Protein phosphorylation is a key regulator of protein-protein interactions. How does the interactome of a protein change during extracellular stimulations? While many individual examples of phosphorylation-regulated interactions were described previously, studies addressing the interactome changes induced by a particular phosphorylation event remain scarce. Here, we try to answer this question, by focusing on interactions between a phosphorylable PDZ-binding linear motif and the entire complement of human PDZ domains. Using a combination of in vitro quantitative techniques and cell-based approaches, we demonstrate that the activation of the mitotic effector kinase RSK1 causes dramatic changes in its connectivity with PDZ domain containing proteins. These changes consist of modulations of the binding affinity of numerous interactions, rather than on/off switching of a few interactions. Our results highlight the previously unappreciated role of phosphorylation in the complex and subtle rewiring of large numbers of protein-protein interactions.