Rewiring of RSK-PDZ interactions by linear motif phosphorylation

Gogl, G.; Biri-Kovacs, B.; Durbesson, F.; Jane, P.; Nomine, Y.; Kostmann, C.; Bilics, V.; Simon, M.; Remenyi, A.; Vincentelli, R.; Trave, G.; Nyitray, L.

doi:10.1101/419721

bioRxiv · 10.1101/419721

Rewiring of RSK-PDZ interactions by linear motif phosphorylation

Gogl, G.·Biri-Kovacs, B.·Durbesson, F.·Jane, P.·Nomine, Y.·Kostmann, C.·Bilics, V.·Simon, M.·Remenyi, A.·Vincentelli, R.·Trave, G.·Nyitray, L.

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Abstract

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.

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Gogl, G., Biri-Kovacs, B., Durbesson, F., Jane, P., Nomine, Y., Kostmann, C., Bilics, V., Simon, M., Remenyi, A., Vincentelli, R., Trave, G., Nyitray, L.. 2018-09-17. Rewiring of RSK-PDZ interactions by linear motif phosphorylation. https://doi.org/10.1101/419721

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