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Chemistry & Biology

Publication date: 2009-04-24
Volume: 16 Pages: 365 - 371
Publisher: Elsevier (Cell Press)

Author:

Hendrickx, Annick
Beullens, Monique ; Ceulemans, Hugo ; Den Abt, Tom ; Van Eynde, Aleycle ; Nicolaescu, Emilia ; Lesage, Bart ; Bollen, Mathieu

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, STRUCTURAL BASIS, CATALYTIC SUBUNIT, IN-VIVO, INHIBITOR-2, BINDING, Animals, Cell Line, Cell Polarity, Computational Biology, Humans, Mice, Protein Interaction Domains and Motifs, Protein Interaction Mapping, Protein Phosphatase 1, Rats, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 0601 Biochemistry and Cell Biology, Organic Chemistry, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry

Abstract:

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.