A Consensus Binding Motif for the PP4 Protein Phosphatase

Yumi Ueki, Thomas Kruse, Melanie Bianca Weisser, Gustav N Sundell, Marie Sofie Yoo Larsen, Blanca Lopez Mendez, Nicole P Jenkins, Dimitriya H Garvanska, Lauren Cressey, Gang Zhang, Norman Davey, Guillermo Montoya, Ylva Ivarsson, Arminja N Kettenbach, Jakob Nilsson

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44 Citations (Scopus)

Abstract

Dynamic protein phosphorylation constitutes a fundamental regulatory mechanism in all organisms. Phosphoprotein phosphatase 4 (PP4) is a conserved and essential nuclear serine and threonine phosphatase. Despite the importance of PP4, general principles of substrate selection are unknown, hampering the study of signal regulation by this phosphatase. Here, we identify and thoroughly characterize a general PP4 consensus-binding motif, the FxxP motif. X-ray crystallography studies reveal that FxxP motifs bind to a conserved pocket in the PP4 regulatory subunit PPP4R3. Systems-wide in silico searches integrated with proteomic analysis of PP4 interacting proteins allow us to identify numerous FxxP motifs in proteins controlling a range of fundamental cellular processes. We identify an FxxP motif in the cohesin release factor WAPL and show that this regulates WAPL phosphorylation status and is required for efficient cohesin release. Collectively our work uncovers basic principles of PP4 specificity with broad implications for understanding phosphorylation-mediated signaling in cells.

Translated title of the contributionEt bindings motiv for PP4 fosfatasen: NA
Original languageEnglish
JournalMolecular Cell
Volume76
Issue number6
Pages (from-to)953-964.e6
ISSN1097-2765
DOIs
Publication statusPublished - 2019

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