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3.6 Type 1 Protein Phosphatase (PP1)
The Ser/Thr-phosphatase PP1 is a ubiquitous and highly conserved eukaryotic pro-
tein that is involved in the regulation of a large variety of cellular processes. There
exist four different but highly similar isoforms of the PP1 catalytic subunit, PP1α,
PP1β/δ, PP1γ1 and PP1γ2, which show different tissue expression patterns and can
have, despite their high similarity, isoform-specific functions (Sasaki et al. 1990 ;
Shima et al. 1993 ). Since the initial identification of PP1 as a phosphatase that
dephosphorylates enzymes of the glycogen metabolism pathway, it has been identi-
fied as a regulatory factor in cellular processes as diverse as protein synthesis, DNA
replication, mitosis, DNA damage response, apoptosis, energy metabolism, muscle
contraction and modulation of signalling processes (Ceulemans and Bollen 2004 ;
Antoniw et al. 1977 ; Kobayaski et al. 1975 ). Like for type 2 phosphatases, the diver-
sified skillset of PP1 stems from the combinatorial assembly of a catalytic subunit
with a regulatory subunit and, occasionally, the formation of a higher order
complex.
3.6.1 PP1-Interacting Proteins (PIPs)
The PP1-interacting proteins (PIPs), of which at least 200 are validated, regulate the
substrate specificity, localisation and activity of PP1 (Virshup and Shenolikar 2009 ;
Heroes et al. 2013 ). PP1 can interact with many different partners—substrates and
regulators—because they all use combinations of the same binding motifs, e.g. 90
% of the PIPs contain a ‘RVxF’ motif that binds to a hydrophobic channel on PP1
(Heroes et al. 2013 ). Other motifs shared by various PIPs are the ‘SILK’ and the
‘MyPhone’ motifs (Heroes et al. 2013 ; Roy and Cyert 2009 ), and it is likely that the
analysis of the binding mode of PIPs will identify further motifs.
Binding of the PIP Repo-Man (recruits PP1 onto mitotic chromatin at ana-
phase) targets PP1 to histone H3 where it counteracts the phosphorylation of his-
tone H3 by the kinase Haspin (Qian et al. 2011 ). Since Aurora-B as part of the
chromosomal passenger complex (CPC) is recruited to Haspin-phosphorylated
histone H3, the activity of PP1/Repo-Man thus contributes to the regulation of
Aurora-B kinase recruitment to centromeres in mitosis. By interacting with other
PIPs, PP1 opposes the function of Aurora-B by alternative mechanisms: Sds22
targets PP1 to the kinetochore protein Knl1, where it suppresses the function of
Aurora-B by dephosphorylating the kinase itself at its activation loop and sub-
strate proteins of Aurora-B (Eiteneuer et al. 2014 ; Kim et al. 2010 ; Liu et al. 2010 ;
Posch et al. 2010 ). These are just two out of many examples of how the binding
of a PIP to PP1 confers specificity for a distinct cellular process to the
holoenzyme.
A. Heim et al.