Docking motif-guided mapping of the interactome of protein phosphatase-1.
The ubiquitous protein Ser/Thr phosphatase-1 (PP1) interacts with dozens of regulatory proteins that are structurally unrelated. However, most of them share a short, degenerate "RVxF"-type docking motif. Using a broad in silico screening based on a stringent definition of the RVxF motif, in combination with a multistep biochemical validation procedure, we have identified 78 novel mammalian PP1 interactors. A global analysis of the validated RVxF-based PP1 interactome not only provided insights into the conserved features of the RVxF motif but also led to the discovery of additional common PP1 binding elements, described as the "SILK" and "MyPhoNE" motifs. In addition to the doubling of the known mammalian PP1 interactome, our data contribute to the design of PP1 interaction networks. Notably, an interaction network linking PP1 interactors discloses a pleiotropic role of PP1 in cell polarity.
Hendrickx
Annick
A
Laboratory of Biosignaling and Therapeutics, Department of Molecular Cell Biology, Faculty of Medicine, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Beullens
Monique
M
Ceulemans
Hugo
H
Den Abt
Tom
T
Van Eynde
Aleyde
A
Nicolaescu
Emilia
E
Lesage
Bart
B
Bollen
Mathieu
M
D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D019295:Computational Biology / Q000379:methods; D006801:Humans; D051379:Mice; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods*; D054645:Protein Phosphatase 1 / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats
D054645:Protein Phosphatase 1