Phosphorylation and inactivation of protein phosphatase 1 by cyclin-dependent kinases.
Open accessAbstract
Protein phosphatase 1 and protein phosphatase 2A contain potential phosphorylation sites for cyclin-dependent kinases. In the present study we found that rabbit skeletal muscle protein phosphatase 1, as well as recombinant protein phosphatase 1 alpha and protein phosphatase 1 gamma 1, but not protein phosphatase 2A, was phosphorylated and inhibited by cdc2/cyclin A and cdc2/cyclin B. Phosphopeptide mapping and phospho amino acid analysis suggested that the phosphorylation site was located at a C-terminal threonine. Neither cdc2/cyclin A nor cdc2/cyclin B phosphorylated an active form of protein phosphatase 1 alpha in which Thr-320 had been mutated to alanine, indicating that the phosphorylation occurred at this threonine residue. Furthermore, protein phosphatase 1, but not protein phosphatase 2A, activity was found to change during the cell cycle of human MG-63 osteosarcoma cells. The observed oscillations in protein phosphatase 1 activity during the cell cycle may be due, at least in part, to phosphorylation of protein phosphatase 1 by cyclin-dependent kinases. Together, the results suggest a mechanism for direct regulation of protein phosphatase 1 activity.
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Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates
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“We determined the efficiency and specificity of these inhibitors by monitoring the level of Thr320 phosphorylation on the PP1 catalytic subunit α (p-PP1α) [24] and of Tyr307 phosphorylation on the PP2A catalytic subunit (p-PP2A) by immunoblotting with appropriate antibodies [25].”
Background
- Authors
- Dohadwala, M., da Cruz e Silva, E. F., Hall, F. L., Williams, R. T., Carbonaro-Hall, D. A., Nairn, A. C., Greengard, P., & Berndt, N.
- Affiliations
- University of Southern California (US)
- Department of Pediatrics, Childrens Hospital Los Angeles, University of Southern California 90027.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-07-05
- Volume
- 91
- Issue
- 14
- Pages
- 6408-6412
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44211
- OpenAlex
- W1989524887
- Cited by
- 259
- References
- 55
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 14 · 2020: 13 · 2019: 12 · 2018: 9 · 2017: 7 · 2016: 7 · 2015: 5 · 2014: 4 · 2013: 8 · 2012: 10
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH40899, P01MH040899)
- 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 1, cyclin-dependent kinases, Cdc2/cyclin B, protein phosphorylation, enzyme inactivation, PP1α, protein phosphatase 2A, cell cycle regulation, skeletal muscle, osteosarcoma cells, phosphopeptide mapping
- MeSH terms
- Amino Acids, Animals, Base Sequence, Bone Neoplasms, Cell Cycle, Cell Line, Cloning, Molecular, Humans, Kinetics, Molecular Sequence Data, Muscles, Oligodeoxyribonucleotides, Peptide Mapping, Phosphopeptides, Phosphoprotein Phosphatases, Phosphorylation, Rabbits, Recombinant Proteins, Osteosarcoma, Tumor Cells, Cultured, CDC2 Protein Kinase, Cyclins, Mutagenesis, Site-Directed, Protein Phosphatase 1, Protein Phosphatase 2
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