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Cited by 134Protein Tyrosine PhosphatasesProtein Kinase Regulation and GTPase SignalingSignaling Pathways in Disease

Protein phosphatase 2A subunit assembly: The catalytic subunit carboxy terminus is important for binding cellular B subunit but not polyomavirus middle tumor antigen

Ogris, Egon, Gibson, Daryl M, Pallas, David C·1997·Oncogene
DOI 10.1038/sj.onc.1201259
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Abstract

The carboxy terminus of protein phosphatase 2A (PP2A) catalytic subunit is highly conserved. Seven out of the last nine residues, including two potential in vivo phosphorylation sites, threonine 304 and tyrosine 307, are completely invariant in all known PP2As. Mutational analysis of the carboxy terminus in vivo was facilitated by efficient immunoprecipitation of trimeric PP2A holoenzyme via an epitope-tagged catalytic subunit. The results indicate that the catalytic subunit carboxy terminus is important for complex formation with the PP2A 55 kDa regulatory B subunit, but not with polyomavirus oncogene, middle tumor antigen (MT), a viral B-type regulatory subunit. Replacing catalytic subunit threonine 304 or tyrosine 307 with a negatively charged amino acid abolished binding of the B subunit to the dimeric enzyme core and altered substrate specificity. Certain other amino acid substitutions of different size and/or charge also abolished or greatly reduced B subunit binding. Substitution of alanine at position 304 or phenylalanine at position 307 did not dramatically reduce B subunit binding or phosphatase activity in vitro, yet the latter substitutions are not found in naturally occurring PP2As. Thus, the wild-type residues are important for a yet unknown function in vivo. Additionally, deleting the carboxy terminal nine amino acids inhibited binding of the B subunit to the dimeric enzyme core, indicating a requirement for one or more of these amino acids for complex formation. MT interaction with the dimeric PP2A enzyme core was not inhibited by any of these mutations. Finally, unlike B subunit, MT does not activate the phosphatase activity of the PP2A heterodimer towards cdc2-phosphorylated histone H1.

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Crossref · 10.1038/sj.onc.1201259

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  • Mutation or deletion of residues 304-309 in the C-terminal tail prevents B55 from binding the PP2A core enzyme.

    “In fact, mutation and deletion of a small region in the C-terminal tail (residues 304–309) was found to abrogate binding between B55 and the core enzyme (Ogris et al., 1997).”

    From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Ogris et al., 1997

  • Reversible methylation of residue L309 at the C-terminal tail of the PP2A catalytic subunit appears critical in modulating the binding affinity of the regulatory subunit and contributing to distinct heterotrimeric complexes.

    “Initial studies have pointed to the reversible methylation of a specific residue (L309) at the C-terminal tail of the catalytic subunit [ 63 – 65 ]. This modification appears to be critical in modulating the binding affinity of the regulatory subunit, contributing to the formation of distinct heterotrimeric complexes.”

    From Targeting PP2A in cancer: an underrated option (2025) · cites this paper as [63]

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Authors
Ogris, E., Gibson, D. M., & Pallas, D. C.
Affiliations
  • Harvard University (US)
  • University of Vienna (AT)
ORCID
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
1997-08-21
Volume
15
Issue
8
Pages
911-917
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
DOI
10.1038/sj.onc.1201259
OpenAlex
W2325151665
Cited by
134
References
1
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 9
FWCI
1.41
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (CA57327, R01CA057327)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
protein phosphatase 2A, protein-protein binding, phosphatase substrate specificity, phosphatase activation
MeSH terms
Animals, Antigens, Neoplasm, Antigens, Viral, Binding Sites, Phosphoprotein Phosphatases, Phosphorylation, Polyomavirus, Precipitin Tests, Substrate Specificity, Threonine, Tyrosine, Mutagenesis, Site-Directed, 3T3 Cells, Mice, Protein Phosphatase 2

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