Recent insights into Protein Phosphatase 2A structure and regulation: the reasons why PP2A is no longer considered as a lazy passive housekeeping enzyme by ProQuest


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 S E        Biotechnol. Agron. Soc. Environ. 2010 14(1), 243-252                                                      Focus on:

Recent insights into Protein Phosphatase 2A structure and
regulation: the reasons why PP2A is no longer considered
as a lazy passive housekeeping enzyme
Maud Martin, Richard Kettmann, Franck Dequiedt
ULg - Gembloux Agro-Bio Tech. Cellular and Molecular Biology Unit. Avenue Maréchal Juin, 13. B-5030 Gembloux
(Belgium). E-mail:

Although intracellular signal transduction is often portrayed as a protein kinase “domino effect”, the counterbalancing function
of phosphatases, and thus the control of phosphatase activity, is equally relevant to proper regulation of cellular function.
Protein Phosphatase 2A (PP2A) is a widely expressed family of protein phosphatases made of a core dimer, composed of a
catalytic (C) subunit and a structural (A) subunit, in association with a third variable regulatory (B) subunit. Although viewed
as a constitutive housekeeping enzyme in the past, PP2A is a highly regulated phosphatase and is emerging as an important
regulator of multiple cellular processes involving protein phosphorylation. The regulation of PP2A is mainly accomplished
by the identity of the regulatory B-type subunit, which determines substrate specificity, subcellular localization and catalytic
activity of the PP2A holoenzyme. In agreement with this, recent findings on the structure and post-translational modifications
of PP2A emphasize the importance of PP2A holoenzyme composition in its regulation and pleiotropic activities.
Keywords. Phosphatase, PP2A, structure, holoenzyme composition, regulatory subunits, regulation.

Nouvelles avancées dans la structure et la régulation de la Protéine Phosphatase 2A : les raisons pour lesquelles PP2A
ne doit plus être considérée comme une enzyme passive et non spécifique. La phosphorylation réversible de protéines
régulatrices intervient dans virtuellement tous les processus biologiques chez les organismes supérieurs. La Protéine Phosphatase
2A (PP2A) est une phosphatase très abondante composée d’un noyau dimérique contenant une sous-unité catalytique (C),
une sous-unité structurale (A) et auquel est associé une sous-unité régulatrice (B) variable. Bien que considérée dans le
passé comme une enzyme constitutive non spécifique, PP2A est une phosphatase soumise à une régulation précise et qui
est importante dans le contrôle des fonctions cellulaires impliquant la phosphorylation. Cette régulation est principalement
accomplie par l’identité de la sous-unité régulatrice qui détermine la spécificité de substrat, la localisation cellulaire et l’activité
catalytique de l’holoenzyme PP2A. Les nouvelles avancées sur le sujet, particulièrement sur la structure et la régulation basée
sur des modifications post-traductionnelles de PP2A, soulignent bien l’importance de la composition de l’holoenzyme PP2A
dans les multiples rôles de cette enzyme majeure.
Mots-clés. Phosphatase, PP2A, structure, composition de l’holoenzyme, sous-unités régulatrices, régulation.

1. INTRODUCTION                                                           Protein phosphatase 2A (PP2A) is a very
                                                                      abundant – it accounts for as much as 1% of total
Reversible protein phosphorylation is an important                    cellular proteins – ubiquitous and remarkably conserved
regulatory mechanism that controls the activities of                  enzyme. A large and still-growing number of PP2A
a myriad of proteins and is thus involved in virtually                substrates have been identified, which makes PP2A
every major physiological process. In the past, most of               an important player in the regulation of a plethora of
the attention was focused primarily on protein kinases                cellular processes.
and on their regulation, mainly because phosphatases                      This article will review the recent advances in the
were then viewed as simple housekeeping enzymes.                      structure and regulation of this fascinating enzyme.
But advances in the understanding of protein
phosphatases make now clear that these enzymes are                    2. CLASSIFICATION
precisely regulated and are as important as kinases in
the regulation of cellular processes involving protein                While proteins can be phosphorylated on nine amino
phosphorylation.                                                      acids, serine, threonine and tyrosine phosphorylation
244      Biotechnol. Agron. Soc. Environ. 2009 13(2), 243-252                      Martin M., Kettmann R. & Dequiedt F.

are by far the most predominant in eukaryotic cells.            et al., 1998; 2003). Within the PP2A holoenzyme,
The enzymes that dephosphorylate these three amino              the PR65/A subunit functions as a scaffold for the
acids are classified into four groups on the basis of            recruitment of the C and B-type subunits as well as
specific catalytic signatures/domain sequences and               additional proteins. The structural PR65/A subunit
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