The extended PP1 toolkit: designed to create specificity.
Protein Ser/Thr phosphatase-1 (PP1) catalyzes the majority of eukaryotic protein dephosphorylation reactions in a highly regulated and selective manner. Recent studies have identified an unusually diversified PP1 interactome with the properties of a regulatory toolkit. PP1-interacting proteins (PIPs) function as targeting subunits, substrates and/or inhibitors. As targeting subunits, PIPs contribute to substrate selection by bringing PP1 into the vicinity of specific substrates and by modulating substrate specificity via additional substrate docking sites or blocking substrate-binding channels. Many of the nearly 200 established mammalian PIPs are predicted to be intrinsically disordered, a property that facilitates their binding to a large surface area of PP1 via multiple docking motifs. These novel insights offer perspectives for the therapeutic targeting of PP1 by interfering with the binding of PIPs or substrates.
Bollen
Mathieu
M
Laboratory of Biosignaling & Therapeutics, Department of Molecular Cell Biology, University of Leuven, B-3000 Leuven, Belgium. Mathieu.Bollen@med.kuleuven.be
Peti
Wolfgang
W
Ragusa
Michael J
MJ
Beullens
Monique
M
D020816:Amino Acid Motifs; D000818:Animals; D020134:Catalytic Domain; D008958:Models, Molecular; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D054645:Protein Phosphatase 1
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