Identification and functional analysis of two Ca2+-binding EF-hand motifs in the B″/PR72 subunit of protein phosphatase 2A
Open accessAbstract
Protein phosphatase 2A (PP2A) is a multifunctional serine/threonine phosphatase that is critical to many cellular processes including cell cycle regulation and signal transduction. PP2A is a heterotrimer containing a structural (A) and catalytic (C) subunit, associated with one variable regulatory or targeting B-type subunit, of which three families have been described to date (B/PR55, B'/PR61, and B"/PR72). We identified two functional and highly conserved Ca(2+)-binding EF-hand motifs in human B"/PR72 (denoted EF1 and EF2), demonstrating for the first time the ability of Ca(2+) to interact directly with and regulate PP2A. EF1 and EF2 apparently bind Ca(2+) with different affinities. Ca(2+) induces a significant conformational change, which is dependent on the integrity of the motifs. We have further evaluated the effects of Ca(2+) on subunit composition, subcellular targeting, catalytic activity, and function during the cell cycle of a PR72-containing PP2A trimer (PP2A(T72)) by site-directed mutagenesis of either or both motifs. The results suggest that integrity of EF2 is required for A/PR65 subunit interaction and proper nuclear targeting of PR72, whereas EF1 might mediate the effects of Ca(2+) on PP2A(T72) activity in vitro and is at least partially required for the ability of PR72 to alter cell cycle progression upon forced expression.
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The B′′ family has three members and requires calcium, through EF-hand motifs, for binding to the PP2A core enzyme.
“Unlike the other three families of regulatory subunits, the B” family possess Ca2+-binding EF-hand motifs as they require the presence of calcium for binding to the PP2A core enzyme (Janssens et al., 2003).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Janssens et al., 2003
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References 52 · Cited by 89
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- Authors
- Janssens, V., Jordens, J., Stevens, I., Van Hoof, C., Martens, E., De Smedt, H., Engelborghs, Y., Waelkens, E., & Goris, J.
- Affiliations
- KU Leuven (BE)
- Corresponding author
- Goris, Jozef
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-03
- Volume
- 278
- Issue
- 12
- Pages
- 10697-10706
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2088587322
- Cited by
- 89
- References
- 52
- Citations by year
- 2025: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 5 · 2013: 6 · 2012: 8
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, cc-by)
- Funders
- KU Leuven
- Vlaamse regering
- 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, EF-hand motifs, calcium binding, conformational change, nuclear targeting, cell cycle progression, site-directed mutagenesis
- MeSH terms
- Amino Acid Sequence, Animals, Calcium, Cell Cycle, Humans, Phosphoprotein Phosphatases, Structure-Activity Relationship, COS Cells, Amino Acid Motifs, Rats, Protein Phosphatase 2
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