Cited by 87PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingProtein Tyrosine Phosphatases

Inhibition of B56-containing Protein Phosphatase 2As by the Early Response Gene IEX-1 Leads to Control of Akt Activity

Open access
Rocher, Gé;raldine, Letourneux, Claire, Lenormand, Philippe, Porteu, Françoise·2007·Journal of Biological Chemistry

Abstract

The importance of PP2A in the regulation of Akt/PKB activity has long been recognized but the nature of the holoenzyme involved and the mechanisms controlling dephosphorylation are not yet known. We identified IEX-1, an early gene product with proliferative and survival activities, as a specific inhibitor of B56 regulatory subunit-containing PP2A. IEX-1 inhibits B56-PP2A activity by allowing the phosphorylation of B56 by ERK. This leads to sustained ERK activation. IEX-1 has no effect on PP2A containing other B family subunits. Thus, studying IEX-1 contribution to signaling should help the discovery of new pathways controlled by B56-PP2A. By using overexpression and RNA interference, we show here that IEX-1 increases Akt/PKB activity in response to various growth factors by preventing Akt dephosphorylation on both Thr(308) and Ser(473) residues. PP2A-B56beta and gamma subunits have the opposite effect and reverse IEX-1-mediated Akt activation. The effect of IEX-1 on Akt is ERK-dependent. Indeed: (i) a IEX-1 mutant deficient in ERK binding had no effect on Akt; (ii) ERK dominant-negative mutants reduced IEX-1-mediated increase in pAkt; (iii) a B56beta mutant that cannot be phosphorylated in the ERK.IEX-1 complex showed an enhanced ability to compete with IEX-1. These results identify B56-containing PP2A holoenzymes as Akt phosphatases. They suggest that IEX-1 behaves as a general inhibitor of B56 activity, enabling the control of both ERK and Akt signaling downstream of ERK.

Integrity signals

Registry

Crossref · 10.1074/jbc.m609712200

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Rocher, G., Letourneux, C., Lenormand, P., & Porteu, F.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Porteu, Françoise
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2007-02
Volume
282
Issue
8
Pages
5468-5477
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2078015812
Cited by
87
References
51
Citations by year
2026: 2 · 2025: 4 · 2024: 1 · 2023: 5 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 5 · 2014: 2 · 2013: 8 · 2012: 4
FWCI
3.43
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Keywords
IEX-1, protein phosphatase 2A, Akt, ERK signaling, Akt dephosphorylation, PP2A holoenzyme, Akt activation, early response genes, growth factor signaling
MeSH terms
Animals, Cricetulus, Enzyme Activation, Cricetinae, Mutation, Phosphoprotein Phosphatases, Phosphorylation, Gene Expression, CHO Cells, Immediate-Early Proteins, MAP Kinase Signaling System, Protein Subunits, RNA Interference, Intercellular Signaling Peptides and Proteins, NIH 3T3 Cells, Protein Modification, Translational, Multiprotein Complexes, Extracellular Signal-Regulated MAP Kinases, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review