Alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure
Abstract
Protein phosphatase 2A (polycation-stimulated protein phosphatase L) was purified from porcine kidney and skeletal muscle. The 36-kDa catalytic and the 65-kDa putative regulatory (hereafter termed PR65) subunits of protein phosphatase 2A2 were separated by reverse-phase HPLC. Partial amino acid sequence data (300 residues) was obtained for PR65. Molecular cloning showed that two distinct mRNAs (termed alpha and beta) encoded the PR65 subunit. The cDNA encoding the alpha-isotype spanned 2.2 kilobases (kb) and contained an open reading frame of 1767 bases predicting a protein of 65 kDa, which was in good agreement with the size of the purified protein. The cDNAs encoding the beta-isotype contained an open reading frame of size similar to that of alpha-form but lacked an initiator ATG. Northern analysis, using RNA isolated from several human cell lines, indicated that the alpha-isotype was encoded by a mRNA of 2.4 kb that was much more abundant than the beta mRNA of 4.0 kb. Comparison of the predicted amino acid sequences of the two isotypes revealed 87% identity. The deduced protein sequences of the alpha- and beta-isotypes were found to be made up of 15 imperfect repeating units consisting of 39 amino acids. This repeating structure was conserved between species.
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The PP2A/Aα and PP2A/Aβ isoforms share about 87% sequence identity.
“There are 2 known isoforms of PP2A/A, PP2A/Aα and PP2A/Aβ, which share approximately 87% sequence identity (Hemmings et al., 1990).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Hemmings et al., 1990
The Aα paralog of PP2A is 10-fold more abundant than the Aβ paralog and is ubiquitously expressed.
“The Aα-paralog is 10-fold more abundant than the Aβ-paralog [ 29 ] and is ubiquitously expressed [ 33 ].”
From Targeting PP2A in cancer: an underrated option (2025) · cites this paper as [29]
The PP2A-A subunit consists of 15 tandem repeats of a conserved 39-residue sequence known as HEAT repeats.
“The PP2A-A subunit consists of 15 tandem repeats of a conserved 39-residue sequence known as the Huntington-elongation-A subunit-TOR (HEAT) repeats (HRs) [ 29 ].”
From Targeting PP2A in cancer: an underrated option (2025) · cites this paper as [29]
The paralogs of PP2A-A (Aα and Aβ) and PP2A-C (Cα and Cβ) share 87% and 98% sequence identity, respectively.
“The paralogs of PP2A-A (Aα and Aβ) and PP2A-C (Cα and Cβ) share 87% and 98% sequence identity, respectively [ 29 , 32 ].”
From Targeting PP2A in cancer: an underrated option (2025) · cites this paper as [29]
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- Authors
- Hemmings, B. A., Adams-Pearson, C., Maurer, F., Mueller, P., Goris, J., Merlevede, W., Hofsteenge, J., & Stone, S. R.
- Affiliations
- Friedrich Miescher Institute (CH)
- ORCID
- Stone, Stuart R.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1990-04-03
- Volume
- 29
- Issue
- 13
- Pages
- 3166-3173
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W1986045037
- Cited by
- 243
- References
- 42
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 8 · 2014: 4 · 2013: 8 · 2012: 3
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- 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, cDNA cloning, mRNA expression, porcine kidney, skeletal muscle, sequence conservation across species
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell Line, DNA, Gene Expression Regulation, Humans, Molecular Sequence Data, Phosphoprotein Phosphatases, Protein Conformation, Repetitive Sequences, Nucleic Acid, RNA, Messenger, Sequence Homology, Nucleic Acid, Swine, Protein Phosphatase 2
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