Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation
Abstract
Extracellular signals that promote cell growth activate cascades of protein kinases. The kinases are dephosphorylated and deactivated by a single type-2A protein phosphatase. The catalytic subunit of type-2A protein phosphatase was phosphorylated by tyrosine-specific protein kinases. Phosphorylation was enhanced in the presence of the phosphatase inhibitor okadaic acid, consistent with an autodephosphorylation reaction. More than 90% of the activity of phosphatase 2A was lost when thioadenosine triphosphate was used to produce a thiophosphorylated protein resistant to autodephosphorylation. Phosphorylation in vitro occurred exclusively on Tyr307. Phosphorylation was catalyzed by p60v-src, p56lck, epidermal growth factor receptors, and insulin receptors. Transient deactivation of phosphatase 2A might enhance transmission of cellular signals through kinase cascades within cells.
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Phosphorylation of T304 and Y307 inhibits PP2A phosphatase activity.
“It has been also shown that modifications to the C-terminus can impact the catalytic activity of the enzyme, as phosphorylation of T304 and Y307 have been shown to inhibit phosphatase activity (Chen et al., 1992; Longin et al., 2007).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Chen et al., 1992
Cites
Transforming gene product of Rous sarcoma virus phosphorylates tyrosine
Hunter, T. R., & Sefton, B. M. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.3.1311 · Cited by 2,333 · see citing works
[42] Detection and quantification of phosphotyrosine in proteins
Cooper, J. A., Sefton, B. M., & Hunter, T. R. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)99075-4 · Cited by 1,109 · see citing works
Anderson, N. G., Maller, J. L., Tonks, N. K., & Sturgill, T. W. (1990) · Nature · doi:10.1038/343651a0 · Cited by 1,064 · see citing works
Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases
Gomez, N. M., & Cohen, P. (1991) · Nature · doi:10.1038/353170a0 · Cited by 580 · see citing works
Pallas, D. C., Shahrik, L. K., Martin, B. L., Jaspers, S. R., Miller, T. B., Brautigan, D. L., & Roberts, T. M. (1990) · Cell · doi:10.1016/0092-8674(90)90726-u · Cited by 573 · see citing works
Self-citationCollett, M. S., Purchio, A. F., & Erikson, R. L. (1980) · Nature · doi:10.1038/285167a0 · Cited by 505 · see citing works
Multiple components in an epidermal growth factor-stimulated protein kinase cascade
Ahn, N. G., Seger, R., Bratlien, R. L., Diltz, C. D., Tonks, N. K., & Krebs, E. G. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)64310-1 · Cited by 492 · see citing works
Ray, L. B., & Sturgill, T. W. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.11.3753 · Cited by 398 · see citing works
Protein phosphatases: recent progress.
Shenolikar, S., & Nairn, A. C. (1991) · PubMed · Cited by 387 · see citing works
The purified product of the transforming gene of avian sarcoma virus phosphorylates tyrosine.
Levinson, A. D., Oppermann, H., VARMUS, H. E., et al. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)70229-4 · Cited by 271 · see citing works
Matsuda, S., Kosako, H., Takenaka, K., Moriyama, K., Sakai, H., Akiyama, T., Gotoh, Y., & Nishida, E. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05136.x · Cited by 265 · see citing works
Identification and characterization of a mitogen-activated S6 kinase.
Jenö, P., Ballou, L. M., Novak‐Hofer, I., & Thomas, G. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.2.406 · Cited by 218 · see citing works
Association of protein phosphatase 2A with polyoma virus medium tumor antigen.
Walter, G., Ruediger, R., Slaughter, C. A., & Mumby, M. C. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.7.2521 · Cited by 209 · see citing works
Mechanism of epidermal growth factor receptor autophosphorylation and high-affinity binding.
Böni‐Schnetzler, M., & Pilch, P. F. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.22.7832 · Cited by 205 · see citing works
Sneddon, A. A., Cohen, P. T. W., & Stark, M. J. R. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07883.x · Cited by 190 · see citing works
Adenosine 5′-0(3-thiotriphosphate) in the control of phosphorytase activity
Gratecos, D., & Fischer, E. H. (1974) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(74)80237-8 · Cited by 190 · see citing works
Haystead, T., Weiel, J. E., Litchfield, D. W., Tsukitani, Y., Fischer, E. H., & Krebs, E. G. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)46261-2 · Cited by 173 · see citing works
Cicirelli, M. F., Pelech, S., & Krebs, E. G. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77978-2 · Cited by 172 · see citing works
Molecular cloning of cDNAs encoding two isoforms of the catalytic subunit of protein phosphatase 2A
Stone, S. R., Hofsteenge, J., & Hemmings, B. A. (1987) · Biochemistry · doi:10.1021/bi00397a003 · Cited by 168 · see citing works
The protein phosphatases involved in cellular regulation
Tung, H. Y. L., Alemany, S., & Cohen, P. (1985) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1985.tb08833.x · Cited by 164 · see citing works
Luttrell, D. K., Luttrell, L. M., & Parsons, S. J. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.1.497-501.1988 · Cited by 146 · see citing works
Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes.
Ariño, J., Woon, C.-W., Brautigan, D. L., Miller, T. B., & Johnson, G. L. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.12.4252 · Cited by 130 · see citing works
Self-citationChung, J., Pelech, S., & Blenis, J. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.11.4981 · Cited by 119 · see citing works
Ballou, L. M., Siegmann, M., & Thomas, G. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.19.7154 · Cited by 117 · see citing works
Three distinct forms of type 2A protein phosphatase in human erythrocyte cytosol.
Usui, H., Imazu, M., Maeta, K., Tsukamoto, H., Azuma, K., & Takeda, M. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68988-4 · Cited by 113 · see citing works
Kyriakis, J. M., Brautigan, D. L., Ingebritsen, T. S., et al. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99183-0 · Cited by 108 · see citing works
Self-citationResolution and reassociation of three distinct components from pig heart phosphoprotein phosphatase.
Imaoka, T., Imazu, M., Usui, H., et al. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)33017-5 · Cited by 97 · see citing works
Tamura, S., KIKUCHI, H., Kikuchi, K., Hiraga, A., & Tsuiki, S. (1980) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1980.tb04435.x · Cited by 87 · see citing works
Kamibayashi, C., Estes, R., Slaughter, C. A., & Mumby, M. C. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98831-9 · Cited by 77 · see citing works
Price, D. J., Gunsalus, J. R., & Avruch, J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.20.7944 · Cited by 67 · see citing works
Sanghera, J. S., Paddon, H. B., & Pelech, S. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)89555-6 · Cited by 64 · see citing works
A second catalytic subunit of type‐2A protein phosphatase from rabbit skeletal muscle
Silva, O. A. B. D. C. E., & Cohen, P. T. W. (1987) · FEBS Letters · doi:10.1016/0014-5793(87)80574-4 · Cited by 56 · see citing works
Phosphotyrosine in proteins. Stability and quantification.
Martensen, T. M. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34121-8 · Cited by 53 · see citing works
Roome, J. M., O'Hare, T., Pilch, P. F., et al. (1988) · Biochemical Journal · doi:10.1042/bj2560493 · Cited by 49 · see citing works
Bodnar, T. W., Coman, G., LACROCE, S. J., et al. (1981) · Journal of the American Chemical Society · doi:10.1021/ja00399a083 · Cited by 47 · see citing works
Li, H., Simonelli, P. F., & Huan, L. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(88)59035-3 · Cited by 18 · see citing works
Insulin stimulates the activity of a protamine kinase in isolated rat hepatocytes.
Reddy, S. A., Amick, G. D., Cooper, R., et al. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38992-6 · Cited by 11 · see citing works
An insulin-stimulated kemptide kinase purified from rat liver is deactivated by phosphatase 2A
Klarlund, J. K., Jaspers, S. R., Khalaf, N., et al. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)64284-3 · Cited by 9 · see citing works
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Cho, U. S., & Xu, W. (2007) · Nature · doi:10.1038/nature05351 · Cited by 459 · see citing works
PP2A holoenzyme assembly: In cauda venenum (the sting is in the tail)
Janssens, V., Longin, S., & Goris, J. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.12.004 · Cited by 390 · see citing works
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Sontag, J.-M., & Sontag, E. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00016 · Cited by 304 · see citing works
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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. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.14.6408 · Cited by 259 · see citing works
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Apostolidis, S. A., Rodríguez-Rodríguez, N., Suárez-Fueyo, A., Dioufa, N., Ozcan, E., Crispín, J. C., Tsokos, M. G., & Tsokos, G. C. (2016) · Nature Immunology · doi:10.1038/ni.3390 · Cited by 238 · see citing works
Calin, G. A., di Iasio, M. G., Caprini, E., Vorechovsky, I., Natali, P. G., Sozzi, G., Croce, C. M., Barbanti-Brodano, G., Russo, G., & Negrini, M. (2000) · Oncogene · doi:10.1038/sj.onc.1203389 · Cited by 219 · see citing works
Sents, W., Ivanova, E., Lambrecht, C., Haesen, D., & Janssens, V. (2013) · The FEBS Journal · doi:10.1111/j.1742-4658.2012.08579.x · Cited by 204 · see citing works
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Sablina, A. A., Hector, M., Colpaert, N., & Hahn, W. C. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2855 · Cited by 193 · see citing works
Moreno, C. S., Park, S., Nelson, K., Ashby, D., Hubalek, F., Lane, W. S., & Pallas, D. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.8.5257 · Cited by 194 · see citing works
Ogris, E., Du, X., Nelson, K. C., Mak, E. K., Yu, X. X., Lane, W. S., & Pallas, D. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.20.14382 · Cited by 191 · see citing works
Longin, S., Zwaenepoel, K., Louis, J. V., Dilworth, S., Goris, J., & Janssens, V. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704059200 · Cited by 184 · see citing works
Büscher, D., Hipskind, R. A., Krautwald, S., Reimann, T., & Baccarini, M. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.1.466 · Cited by 176 · see citing works
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Gourmaud, S., Shou, H., Irwin, D. J., Sansalone, K., Jacobs, L. M., Lucas, T. H., Marsh, E. D., Davis, K. A., Jensen, F. E., & Talos, D. M. (2020) · Brain · doi:10.1093/brain/awz381 · Cited by 155 · see citing works
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Switzer, C. H., Glynn, S. A., Cheng, R. Y.-S., Ridnour, L. A., Green, J. E., Ambs, S., & Wink, D. A. (2012) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-12-0124 · Cited by 141 · see citing works
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Liu, R., Zhou, X. ‐., Tanila, H., Bjorkdahl, C., Wang, J. ‐., Guan, Z. ‐., Cao, Y., Gustafsson, J. ‐., Winblad, B., & Pei, J. ‐. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00249.x · Cited by 125 · see citing works
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Xiong, Y., Jing, X.-P., Zhou, X.-W., Wang, X.-L., Yang, Y., Sun, X.-Y., Qiu, M., Cao, F.-Y., Lu, Y.-M., Liu, R., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.07.003 · Cited by 122 · see citing works
Targeting Inhibitors of the Tumor Suppressor PP2A for the Treatment of Pancreatic Cancer
Farrell, A. S., Allen-Petersen, B., Daniel, C. J., Wang, X., Wang, Z., Rodriguez, S., Impey, S., Oddo, J., Vitek, M. P., Lopez, C., et al. (2014) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-13-0542 · Cited by 114 · see citing works
Arnold, H. K., & Sears, R. C. (2008) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9128-9 · Cited by 111 · see citing works
Riehle, C., Wende, A. R., Zhu, Y., Oliveira, K. J., Pereira, R. O., Jaishy, B. P., Bevins, J., Valdez, S., Noh, J., Kim, B. J., et al. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00426-14 · Cited by 105 · see citing works
Ugi, S., Imamura, T., Ricketts, W., & Olefsky, J. M. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.2375-2387.2002 · Cited by 95 · see citing works
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McConnell, J. L., Gomez, R. J., McCorvey, L. R. A., Law, B. K., & Wadzinski, B. E. (2007) · Oncogene · doi:10.1038/sj.onc.1210406 · Cited by 80 · see citing works
Switzer, C. H., Glynn, S. A., Ridnour, L. A., Cheng, R. Y.-S., Vitek, M. P., Ambs, S., & Wink, D. A. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.07.001 · Cited by 74 · see citing works
Kauko, O., Laajala, T. D., Jumppanen, M., Hintsanen, P., Suni, V., Haapaniemi, P., Corthals, G., Aittokallio, T., Westermarck, J., & Imanishi, S. Y. (2015) · Scientific Reports · doi:10.1038/srep13099 · Cited by 61 · see citing works
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Nardi, F., Lipina, C., Magill, D., Hage Hassan, R., Hajduch, E., Gray, A., & Hundal, H. S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092255 · Cited by 36 · see citing works
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MacKay, K. B., Tu, Y., Young, S. G., & Clarke, S. G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065967 · Cited by 14 · see citing works
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- Authors
- Chen, J., Martin, B. L., & Brautigan, D. L.
- Affiliations
- Brown University (US)
- Venue
- Science
- Published
- 1992-08-28
- Volume
- 257
- Issue
- 5074
- Pages
- 1261-1264
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1997664222
- Cited by
- 601
- References
- 38
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 10 · 2021: 14 · 2020: 13 · 2019: 17 · 2018: 9 · 2017: 25 · 2016: 26 · 2015: 23 · 2014: 31 · 2013: 30 · 2012: 38
- FWCI
- 8.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (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, tyrosine phosphorylation, okadaic acid, p60v-src, Lck, epidermal growth factor receptor, insulin receptor, protein kinase cascades, signal transduction, catalytic subunit
- MeSH terms
- Animals, Ethers, Cyclic, Gene Expression Regulation, Humans, Phosphoprotein Phosphatases, Phosphorylation, Protein-Tyrosine Kinases, Rabbits, Receptor, Insulin, Thionucleotides, Tyrosine, Oncogene Protein pp60(v-src), Okadaic Acid, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Protein Phosphatase 2, ErbB Receptors, In Vitro Techniques
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