Protein phosphatase 2A: Variety of forms and diversity of functions

• Autorzy: Lechward K. , Awotunde O.S. , Swiatek W. , Muszynska G.
• Języki publikacji: EN

Abstrakty

EN

Protein phosphatase 2A (PP2A) comprises a diverse family of phosphoserine- and phosphothreonine-specific phosphatases present in all eukaryotic cells. All forms of PP2A contain a catalytic subunit (PP2Ac) which forms a stable complex with thestructural subunit PR65/A. The heterodimer PP2Ac-PR65/A associates with regulatory proteins, termed variable subunits, in order to form trimeric holoenzymes attributed with distinct substrate specificity and targeted to different subcellular compartments. PP2Ac activity can be modulated by reversible phosphorylation on Tyr307 and methylation on C-terminal Leu309. Studies on PP2A have shown that this enzyme may be implicated in the regulation of metabolism, transcription, RNA splicing, translation, differentiation, cell cycle, oncogenic transformation and signal transduction.

Słowa kluczowe

EN

reversible phosphorylation; protein phosphatase; cell cycle; phosphorylation; protein-protein interaction; carcinogenesis; signal transduction

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2001
• Tom: 48
• Numer: 4
• Opis fizyczny: p.921-933,fig.

Twórcy

autor

Lechward K.

• University of Gdansk, Gdansk, Poland

autor

Awotunde O.S.

autor

Swiatek W.

autor

Muszynska G.

Bibliografia

• 1.Krebs,E. (1986) The enzymology of control by phosphorylation. Enzymes 17, 3-20.
• 2.Mumby,M.C. & Walter, G. (1993) Protein serine/threonine phosphatases: Structure, regulation and functions in cell growth. Physiol. Rev. 73, 673-692.
• 3.Oliver, C.J. & Shenolikar, S. (1998) Physiological importance of protein phosphatase inhibitors. Front. Biosci. 3, D961-972.
• 4.Hunter, T. (1995) Protein kinases and phosphatases: The yin and yang of protein phosphorylation and signalling. Cell 80, 225-236.
• 5.Shenolikar, S. (1994) Protein serine/threonine phosphatases — new avenues for cell regulation. Annu. Rev. Cell Biol. 10, 55-86.
• 6.Barford,D. (1996) Molecular mechanisms of the protein serine/threonine phosphatases. Trends Biochem. Sci. 21, 407-412.
• 7.Wera,S. & Hemmings, B.A. (1995) Serine/ threonine phosphatases. Biochem. J. 311, 17-29.
• 8.Millward,T.A., Zolnierowicz, S. & Hemmings, B.A. (1999) Regulation of protein kinase cascades by protein phosphatase 2A. Trends Biochem. Sci. 24, 186-191.
• 9.Cohen,P.T. (1997) Novel protein serine/threonine phosphatases: Variety is the spice of life. Trends Biochem. Sci. 22, 245-251.
• 10.Zolnierowicz,S. (2000) Type 2A protein phosphatase, the complex regulator of numerous signalling pathways. Biochem. Pharmacol. 60, 1225-1235.
• 11.Andjelkovic,N., Zolnierowicz, S., Mayer- Jaekel, R.E. & Hemmings, B.A. (1996) Structure, regulation and targeting of protein phosphatase 2A; in: NATO ASISeries; vol. H102, I nteractingprotein domains, their role in signal and energy transduction (Heilmeyer, L., ed.) pp. 196-205, Springer-Verlag Berlin, Heidelberg.
• 12.Mayer-Jaekiel,R.E. & Hemmings, B.A. (1994) Protein phosphatase type 2A-menage a trois. Trends Cell Biol. 4, 287-291.
• 13.Mayer,R.E., Khew-Goodall, Y., Stone, S.R. & Hemmings, B.A.(1991) Structure and expression of protein phosphatase PP2A. Adv. Prot. Phosphatases 6, 125-143.
• 14.Groves,M.R., Hanlon, N., Turowski, P., Hemmings, B.A. & Barford, D. (1999) The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs. Cell 96, 99-110.
• 15.Moreno,C.S., Park, S., Nelson, K., Ashby, D., Hubalek, F., Lane, W.S. & Pallas, D.C. (2000) WD40 repeat proteins striatin and S/G(2) nuclear autoantigen are members of a novel family of calmodulin-binding proteins that associate with protein phosphatase 2A. J. Biol. Chem. 275, 5257-5263.
• 16.Zolnierowicz,S., Van Hoof, C., Andjelkovic, N., Cron, P., Stevens, J., Merlevede, W., Goris, J. & Hemmings, B.A. (1996) The variable subunit associated with protein phosphatases 2A0 defines a novel multimember family of regulatory subunits. Biochem. J. 317, 187-194.
• 17.Healy,A.M., Zolnierowicz, S., Stapleton, A.E., Goebl, M., DePaoli-Roach, A.A. & Pringle, J.R. (1991) CDC55, a Saccharomyces cerevisiae gene involved in cellular morphogenesis: Identification, characterization and homology to the B subunit of mammalian type 2A protein phosphatase. Mol. Cell. Biol. 11, 5767-5780.
• 18.Mayer-Jaekel,R.E., Ohkura, H., Gomes, R., Sunkel, C.E., Baumgartner, S., Hemmings, B.A. & Glover, D.M. (1993) The 55 kd regulatory subunit of Drosophila protein phosphatase 2A is required for anaphase. Cell 72, 621-633.
• 19.Turowski,P., Myles, T., Hemmings, B.A., Fernandez, A. & Lamb, N.J. (1999) Vimentin dephosphorylation by protein phosphatase 2A is modulated by the targeting subunit B55. Mol. Biol. Cell 10, 1997-2015.
• 20.Mayer,R.E., Hendrix, P., Cron, P., Matthies, R., Stone, S.R., Goris, J., Merlevede, W., Hofsteenge, J. & Hemmings, B.A. (1991) Structure of the 55-kDa regulatory subunit of protein phosphatase 2A: Evidence for a neuronal-specific isoform. Biochemistry 30, 3589- 3597.
• 21.McCright,B., Rivers, A.M., Audlin, S. & Virshup, D.M. (1996) The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm. J. Biol. Chem. 271, 22081-22089.
• 22.Graeber,T.G., Peterson, J.F., Tsai, M., Monica, K., Fornace, A., J., Jr. & Giaccia, A., J. (1994) Hypoxia induces accumulation of p53 protein, but activation of a G1-phase checkpoint by low-oxygen conditions is independent of p53 status. Mol. Cell. Biol. 14, 6264-6277.
• 23.Okamoto, K., Kamibayashi, C., Serrano, M., Prives, C., Mumby, M.C. & Beach, D. (1996) p53-dependent association between cyclin G and the B' subunit of protein phosphatase 2A. Mol. Cell. Biol. 16, 6593-6602.
• 24.Li, X., Yost, H.J., Virshup, D.M. & Seeling, J.M. (2001) Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus. EMBO J. 20, 4122-4131.
• 25.Seeling, J.M., Miller, J.R, Gil, R., Moon, R.T., White, R. & Virshup, D.M. (1999) Regulation of beta-catenin signaling by the B56 subunit of protein phosphatase 2A. Science 283, 2089- 2091.
• 26.Cegielska,A., Shaffer, S., Derua, R., Goris, J. & Virshup, D.M. (1994) Different oligomeric forms of protein phosphatase type 2A activate and inhibit simian virus 40 DNA replication. Mol. Cell. Biol. 14, 4616-4623.
• 27.Yan,Z., Fedorov, S.A., Mumby, M.C. & Williams, R.S. (2000) PR48, a novel regulatory subunit of protein phosphatase 2A, interacts with Cdc6 and modulates DNA replication in human cells. Mol. Cell. Biol. 20, 1021-1029.
• 28.Voorhoeve,P.M., Watson, R.J., Farlie, P.G, Bernards, R. & Lam, E.W. (1999) Rapid dephosphorylation of p107 following UV radiation. Oncogene 18, 679-688.
• 29.Kamibayashi,C. & Mumby, M.C. (1995) Control of protein phosphatase 2A by multiple families of regulatory subunits. Adv. Prot. Phosphatases 9, 199-214.
• 30.Pallas,D.C., Shahrik, L.K., Martin, B.L., Jaspers, S., Miller, T.B., Brautigan, D.L. & Roberts, T.M. (1990) Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A. Cell 60, 167-176.
• 31.Walter, G. & Mumby, M.C. (1993) Protein serine/threonine phosphatases and cell transformation. Biochim. Biophys. Acta 1155, 207- 226.
• 32.Kleinberger,T. & Shenk, T. (1993) Adenovirus E4orf4 protein binds to protein phosphatase 2A and the complex down regulates E1A-enhanced junBtranscription. J. Virol. 67, 7556- 7560.
• 33.Tung,H.Y., De Rocquigny, H., Zhao, L.J., Cayla, X., Roques, B.P. & Ozon, R. (1997) Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr. FEBS Lett. 401, 197-201.
• 34.Cowley,S., Paterson, H., Kemp, P. & Marshall, C.J. (1994) Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 77, 841-852.
• 35.Gomez,N. & Cohen, P. (1991) Dissection of the protein kinase cascade by which nerve growth factor activates MAP kinases. Nature 353, 170-173.
• 36.Sontag, E. (2001) Protein phosphatase 2A: The Trojan Horse of cellular signaling. Cell Signal 13, 7-16.
• 37.Sontag, E., Fedorov, S., Kamibayashi, C., Robbins, D., Cobb, M. & Mumby, M.C. (1993) The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the MAP kinase pathway and induces cell proliferation. Cell 75, 887-897.
• 38.Santoro, M.F., Annard, R.R., Robertson, M.M., Peng, Y.W., Brady, M.J., Mankovich, J.A., Hacket, M.C., Ghayur, T., Walter, G., Wong, G.G. & Giegel, D.A. (1998) Regulation of protein phosphatase 2A activity by caspase-3 during apoptosis. J. Biol. Chem. 273, 13119-13128.
• 39.Orth, K., ORourke, K., Salvesen, G.S. & Dixit, V.M. (1996) Molecular ordering of apoptotic mammalian CED-3/ICE-like proteases. J. Biol. Chem. 271, 20977-20980.
• 40.Chen,J., Peterson, R.T. & Schreiber, S.L. (1998) Alpha 4 associates with protein phosphatases 2A, 4 and 6. Biochem. Biophys. Res. Commun. 247, 827-832.
• 41.Murata,K., Wu, J. & Brautigan, D.L. (1997) B cell receptor-associated protein alpha4 displays rapamycin-sensitive binding directly to the catalytic subunit of protein phosphatase 2A. Proc. Natl. Acad. Sci. U.S.A.. 94, 10624- 1069.
• 42.Kawabe, T., Muslin, A.J. & Korsmeyer, S.J. (1997) HOX11 interacts with protein phosphatases PP2A
• and PP1 and disrupts a G2/M cell-cycle checkpoint. Nature 385, 454-458.
• 43.Inoue, R., Usui, H., Tanabe, O., Nishito, Y., Shimizu, M. & Takeda, M. (1999) Studies on functions of the 63-kDa A- and 74-kDa B'(delta)-regulatory subunits in human erythrocyte protein phosphatase 2A: Dissociation and reassociation of the subunits. J. Biochem. 126, 1127-1135.
• 44.Hong,Y. & Sarge, K.D. (1999) Regulation of protein phosphatase 2A activity by heat shock transcription factor 2. J. Biol. Chem. 274, 12967-12970.
• 45.Andjelkovic,N., Zolnierowicz, S., Van Hoof, C., Goris, J. & Hemmings, B.A. (1996) The catalytic subunit of protein phosphatase 2A associates with the translation termination factor eRF1. EMBO. J. 15, 7156-7167.
• 46.Lechward,K., Zolnierowicz, S. & Hemmings, B.A. (1999) Eukaryotic translation termination factor 1 associates with protein phosphatase 2A and targets it to ribosomes. Biochemistry (Moscow) 64, 1373-1381.
• 47.Maniatis,T. (1999) A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless and Hedgehog signaling pathways. Genes Dev. 13, 505-510.
• 48.Gotz,J., Probst, A., Mistl, C., Nitsch, R.M. & Ehler, E. (2000). Distinct role of protein phosphatase 2A subunit C alpha in the regulation of E-cadherin and beta-catenin during development. Mech. Dev. 93, 83-93.
• 49.MacKintosh,C. & MacKintosh, R.W. (1994) Inhibitors of protein kinases and phosphatases. Trends Biochem. Sci. 19, 444-448.
• 50.Evans,D.R. & Simon, J.A. (2001) The predicted beta12-beta13 loop is important for inhibition of PP2Ac alpha by the antitumor drug fostriecin. FEBSLett. 498, 110-115.
• 51.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) Low frequency of alterations of the alpha (PPP2R1A) and beta (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms. Oncogene 19, 1191-1195.
• 52.Wang,S.S., Esplin, E.D., Li, J.L., Huang, L., Gazdar, A., Minna, J. & Evans, G.A. (1998) Alterations of the PPP2R1B gene in human lung and colon cancer. Science 282, 284-287.
• 53.Nigg,E.A. (2001) Mitotic kinases as regulators of cell division and its checkpoints. Nat. Rev. Mol. Cell Biol. 2, 21-32.
• 54.Karaisoku,A., Jessus, C., Brassac, T. & Ozon, R. (1999) Phosphatase 2A and polo kinase, two antagonistic regulators of cdc25 activation and MPF auto-amplification. J. Cell Sci. 112, 3747-3756.
• 55.Li,M., Makkinje, A. & Damuni, Z. (1996) Molecular identification of I1PP2A, a novel potent heat-stable inhibitor protein of protein phosphatase 2A. Biochemistry 35, 6998-7002.
• 56.Li, M., Makkinje, A. & Damuni, Z. (1996) The myeloid leukaemia associated protein SET is a potent inhibitor of protein phosphatase 2A. J. Biol. Chem. 271, 11059-11062.
• 57.Adler, H.T., Nallaseth, F.S., Walter, G. & Tkachuk, D.C. (1997) HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A. J. Biol. Chem. 272, 28407-28414.
• 58.Sontag, E., Nunbhakdi-Craig, V., Lee, G., Brandt, R., Kamibayashi, C., Kuret, J., White, C.L., 3rd, Mumby, M.C. & Bloom, G.S. (1999) Molecular interactions among protein phosphatase 2A, tau and microtubules. Implications for the regulation of tau phosphorylation and the development of tauopathies. J. Biol. Chem. 274, 25490-25498.
• 59.Saito, T., Shima, H., Osawa, Y., Nagao, M., Hemmings, B.A., Kishimoto, T. & Hisanaga, S. (1995) Neurofilament-associated protein phosphatase 2A: Its possible role in preserving neurofilaments in filamentous states. Biochemistry 34, 7376-7384.
• 60.Takahashi,M., Shibata, H., Shimakawa, M., Miyamoto, M., Mukai, H. & Ono, Y. (1999) Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the Golgi apparatus. J. Biol. Chem. 274, 17267-17274.
• 61.Hsu,W., Zeng, L. & Costantini, F. (1999) Identification of a domain of axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain. J. Biol. Chem. 274, 3439-3445.
• 62.Baharians,Z. & Schontal, A.H. (1998) Autoregulation of protein phosphatase type 2A expression. J. Biol. Chem. 273, 19019-19024.
• 63.Swiatek, W., Sugajska, E., Lankiewicz, L. & Zolnierowicz, S. (2000) Biochemical characterization of recombinant subunits of type 2A protein phosphatase overexpressed in Pichia pastoris. Eur. J. Biochem. 267, 5209-5216.
• 64.Chen,J., Parsons, S. & Brautigan, D.L. (1994) Tyrosine phosphorylation of protein phosphatase 2A in response to growth stimulation and v-src transformation of fibroblasts. J. Biol. Chem. 269, 7957-7962.
• 65.Damuni,Z., Xiong, H. & Li, M. (1994) Autophosphorylation-activated protein kinase inactivates the protein tyrosine phosphatase activity of protein phosphatase 2A. FEBSLett. 352, 311-314.
• 66.Favre,B., Zolnierowicz, S., Turowski, P. & Hemmings, B.A., (1994) The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo. J. Biol. Chem. 269, 16311- 16316.
• 67.Wu,J., Tolstykh, T., Lee, J., Boyd, K., Stock, J.B. & Broach, J.R., (2000) Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatory subunits in vivo. EMBO J. 19, 5672-5681.
• 68.Hubbard,M.J. & Cohen, P. (1993) On target with a new mechanism for the regulation of protein phosphorylation. Trends Biochem. Sci. 18, 172-177.