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PPP1R2 (Inhibitor 2) stimulates protein phosphatase PP1 through stabilisation of dynamic subunit interactions

ABSTRACT: Protein Ser/Thr phosphatase PP1 is always associated with one or two regulatory subunits or RIPPOs. One of the earliest evolved RIPPOs is PPP1R2, also known as Inhibitor-2. Since its discovery nearly 5 decades ago, PPP1R2 has been variously described as an inhibitor, activator or (metal) chaperone of PP1, but it is still unknown how PPP1R2 affects the function of PP1 in intact cells. Here, using newly developed research tools, we demonstrate that PPP1R2 stabilizes a subgroup of PP1 holoenzymes, exemplified by PP1:RepoMan, thereby promoting the dephosphorylation of their substrates. Mechanistically, the recruitment of PPP1R2 disrupts the inhibitory, fuzzy interaction between the C-terminal tail and catalytic domain of PP1, and generates an additional C-terminal RepoMan-interaction site. The resulting holoenzyme is further stabilized by a direct PPP1R2:RepoMan interaction, which renders it refractory to competitive disruption by RIPPOs that do not interact with PPP1R2. Our data demonstrate that PPP1R2 modulates the function of PP1 by altering the balance between holoenzymes through stabilisation of specific subunit interactions.

INSTRUMENT(S): LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Rita Derua

LAB HEAD: Prof. Dr. Mathieu Bollen

PROVIDER: PXD052317 | Pride | 2024-11-13

REPOSITORIES: Pride

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			Action	DRS
	M1.raw	Raw
	M10.raw	Raw
	M11.raw	Raw
	M12.raw	Raw
	M2.raw	Raw

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