A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation
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Both F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. Retrotransposon insertion was found to produce an N-terminally truncated form (Deltagamma1) of the B56gamma1 regulatory subunit isoform of protein phosphatase (PP) 2A in BL6 cells, but not in F10 cells. We found an interaction of paxillin with PP2A C and B56gamma subunits by co-immunoprecipitation. B56gamma1 co-localized with paxillin at focal adhesions, suggesting a role for this isoform in targeting PP2A to paxillin. In this regard, Deltagamma1 behaved similarly to B56gamma1. However, the Deltagamma1-containing PP2A heterotrimer was insufficient for the dephosphorylation of paxillin. Transfection with Deltagamma1 enhanced paxillin phosphorylation on serine residues and recruitment into focal adhesions, and cell spreading with an actin network. In addition, Deltagamma1 rendered F10 cells as highly metastatic as BL6 cells. These results suggest that mutations in PP2A regulatory subunits may cause malignant progression.
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The role of B′ subunits as tumor suppressors is corroborated by the notion that B′ subunit knockdown causes polyploidy.
“This notion corroborates with the previous notion on the role of B′ subunits as tumor suppressors [45–49].”
From PP2A-B′ holoenzyme substrate recognition, regulation and role in cytokinesis (2017) · cites this paper as [47]
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Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation
Liotta, L. A., Steeg, P. S., & Stetler‐Stevenson, W. G. (1991) · Cell · doi:10.1016/0092-8674(91)90642-c · Cited by 2,701 · see citing works
FOCAL ADHESIONS, CONTRACTILITY, AND SIGNALING
Burridge, K., & Chrzanowska‐Wodnicka, M. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.463 · Cited by 1,943 · see citing works
Burridge, K., Turner, C. E., & Romer, L. H. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.119.4.893 · Cited by 1,310 · see citing works
Hannigan, G. E., Leung-Hagesteijn, C., Fitz-Gibbon, L., Coppolino, M. G., Radeva, G., Filmus, J., Bell, J. C., & Dedhar, S. (1996) · Nature · doi:10.1038/379091a0 · Cited by 1,100 · see citing works
LEUNG, T. K. C., Chen, X., Manser, E. J., & Lim, L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.10.5313 · Cited by 902 · see citing works
Regulation of protein kinase cascades by protein phosphatase 2A
Millward, T. A., Zołnierowicz, S., & Hemmings, B. A. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01375-4 · Cited by 793 · see citing works
Activation of Rac and Cdc42 by Integrins Mediates Cell Spreading
Price, L., Leng, J., Schwartz, M. A., & Bokoch, G. (1998) · Molecular Biology of the Cell · doi:10.1091/mbc.9.7.1863 · Cited by 644 · see citing works
Serine/threonine protein phosphatases
Wera, S., & Hemmings, B. A. (1995) · Biochemical Journal · doi:10.1042/bj3110017 · Cited by 637 · see citing works
Turner, C. E., Brown, M. C., Perrotta, J. A., Riedy, M. C., Nikolopoulos, S. N., McDonald, A. R., Bagrodia, S., Thomas, S. Μ., & Leventhal, P. S. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.4.851 · Cited by 471 · see citing works
Protein Serine/Threonine Phosphatases—New Avenues for Cell Regulation
Shenolikar, S. (1994) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.10.110194.000415 · Cited by 429 · see citing works
[37] Protein phosphatase-1 and protein phosphatase-2A from rabbit skeletal muscle
Cohen, P., Alemany, S., Therese, B. A., Resink, J., Strålfors, P., & Tung, H. Y. L. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(88)59039-0 · Cited by 411 · see citing works
In vitro selection of murine B16 melanoma variants with enhanced tissue-invasive properties.
Poste, G. H., Doll, J., Hart, I. R., & Fidler, I. J. (1980) · PubMed · Cited by 408 · see citing works
McCright, B., Rivers, A. M., Audlin, S., & Virshup, D. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.36.22081 · Cited by 382 · see citing works
Brown, M. C., Perrotta, J. A., & Turner, C. E. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.135.4.1109 · Cited by 368 · see citing works
Alessi, D. R., Gomez, N., Moorhead, G., Lewis, T., Keyse, S. M., & Cohen, P. (1995) · Current Biology · doi:10.1016/s0960-9822(95)00059-5 · Cited by 365 · see citing works
Bowden, E. T., Barth, M. M., Thomas, D., Glazer, R. I., & Mueller, S. C. (1999) · Oncogene · doi:10.1038/sj.onc.1202827 · Cited by 356 · see citing works
The Intracisternal A-Particle Gene Family: Structure and Functional Aspects
Kuff, E. L., & Lueders, K. K. (1988) · Advances in cancer research · doi:10.1016/s0065-230x(08)60223-7 · Cited by 335 · see citing works
Turner, C. E., & Miller, J. T. (1994) · Journal of Cell Science · doi:10.1242/jcs.107.6.1583 · Cited by 316 · see citing works
Sontag, E., Nunbhakdi‐Craig, V., Bloom, G. S., & Mumby, M. C. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.128.6.1131 · Cited by 301 · see citing works
Favre, B., Turowski, P., & Hemmings, B. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.21.13856 · Cited by 300 · see citing works
Yamashita, K., Yasuda, H., Pines, J., et al. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07882.x · Cited by 279 · see citing works
Sabe, H., Hata, A., Okada, M., Nakagawa, H., & Hanafusa, H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.3984 · Cited by 222 · see citing works
Self-citationTrochon-Joseph, V., Mabilat, C., Bertrand, P., Legrand, Y., Smadja‐Joffe, F., Soria, C., Delpech, B., & Lu, H. (1996) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19960529)66:5 · Cited by 211 · see citing works
Harden, N., Lee, J., Loh, H.-Y., et al. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.5.1896 · Cited by 206 · see citing works
HOX11 interacts with protein phosphatases PP2A and PP1 and disrupts a G2/M cell-cycle checkpoint
Kawabe, T., Muslin, A. J., & Korsmeyer, S. J. (1997) · Nature · doi:10.1038/385454a0 · Cited by 197 · see citing works
Nip, J., Shibata, H. R., Loskutoff, D. J., et al. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116007 · Cited by 172 · see citing works
Malliri, A., Symons, M. H., Hennigan, R. F., Hurlstone, A. F. L., Lamb, R. F., Wheeler, T., & Ozanne, B. W. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.4.1087 · Cited by 155 · see citing works
Brown, M. C., Perrotta, J. A., & Turner, C. E. (1998) · Molecular Biology of the Cell · doi:10.1091/mbc.9.7.1803 · Cited by 141 · see citing works
Identification of a Novel Protein Phosphatase 2A Regulatory Subunit Highly Expressed in Muscle
Tehrani, M. A., Mumby, M. C., & Kamibayashi, C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.9.5164 · Cited by 122 · see citing works
Bellis, S. L., Perrotta, J. A., Curtis, M. S., & Turner, C. E. (1997) · Biochemical Journal · doi:10.1042/bj3250375 · Cited by 116 · 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
Nichilo, M. O. D., & Yamada, K. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.18.11016 · Cited by 111 · see citing works
Regulation of Endosome Sorting by a Specific PP2A Isoform
Molloy, S. S., Thomas, L., Kamibayashi, C., et al. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.6.1399 · Cited by 102 · see citing works
Ito, A., Morii, E., Maeyama, K., et al. (1998) · Blood · doi:10.1182/blood.v91.9.3210 · Cited by 75 · see citing works
Self-citationMazaki, Y., Hashimoto, S., & Sabe, H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.11.7437 · Cited by 65 · see citing works
Self-citationVerschueren, H., der Taelen, I. V., Dewit, J., Braekeleer, J. D., & BAETSELIER, P. D. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.55.4.552 · Cited by 51 · see citing works
Kobori, M., Ikeda, Y., Nara, H., et al. (1998) · Genes to Cells · doi:10.1046/j.1365-2443.1998.00202.x · Cited by 36 · see citing works
Self-citationRegulation of cytoskeletal organization in tumor cells by protein phosphatases‐1 and ‐2A
Maier, G. D., Wright, M. A., Lozano, Y., et al. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910610110 · Cited by 31 · see citing works
Protein phosphatases limit tumor motility
Young, M. R., Lozano, Y., Djorjevic, A., et al. (1993) · International Journal of Cancer · doi:10.1002/ijc.2910540629 · Cited by 22 · see citing works
Perchellet, E. M., Gali, H. U., Gao, X. M., et al. (1993) · International Journal of Cancer · doi:10.1002/ijc.2910550626 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Janssens, V., & Goris, J. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3530417 · Cited by 1,890 · see citing works
Paxillin and focal adhesion signalling
Turner, C. E. (2000) · Nature Cell Biology · doi:10.1038/35046659 · Cited by 839 · see citing works
Brown, M. C., & Turner, C. E. (2004) · Physiological Reviews · doi:10.1152/physrev.00002.2004 · Cited by 601 · see citing works
Deakin, N. O., & Turner, C. E. (2008) · Journal of Cell Science · doi:10.1242/jcs.018044 · Cited by 499 · see citing works
“Journal of Cell Science 121 (15) NCK 118 PY PY LIM1 LIM2 LIM3 LIM4LD2 LD3 LD5LD4LD1 31 Focal-adhesion targeting PY PY PTP-PEST PAK GITPIX FAK and Src kinases Rac1 Cell adhesion or integrin signaling PS 273 PP2A Localized lamellipodium formation Dephosphorylation Paxillin Fig.”
BackgroundInfluentialPhosphatase: PP2A structural importance, regulation and its aberrant expression in cancer
Seshacharyulu, P., Pandey, P., Datta, K., & Batra, S. K. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.02.036 · Cited by 479 · see citing works
“Moreover, association of increased cell motility and invasiveness due to altered PP2A activity was observed in BL6 mouse melanoma cells [65], lung carcinoma [66] and head and neck squamous carcinoma [67].”
BackgroundCrystal structure of a protein phosphatase 2A heterotrimeric holoenzyme
Cho, U. S., & Xu, W. (2007) · Nature · doi:10.1038/nature05351 · Cited by 459 · see citing works
Structure of the Protein Phosphatase 2A Holoenzyme
Xu, Y., Xing, Y., Chen, Y., Chao, Y., Lin, Z., Fan, E., Yu, J. W., Strack, S., Jeffrey, P. D., & Shi, Y. (2006) · Cell · doi:10.1016/j.cell.2006.11.033 · Cited by 450 · see citing works
“…addition, an amino-terminally truncated form of the B subunit PR61/B0g1 was found to be associated with a higher metastatic state of melanoma cells (Ito et al., 2000, 2003; Koma et al., 2004), while gainand loss-of-function experiments firmly established this regulatory subunit as a tumor…”
PP2A: the expected tumor suppressor
Janssens, V., Goris, J., & Van Hoof, C. (2005) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2004.12.004 · Cited by 426 · see citing works
Protein phosphatase 2A: a target for anticancer therapy
Perrotti, D., & Neviani, P. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70558-2 · Cited by 400 · see citing works
Focal adhesions: Structure and dynamics
Petit, V., & Thiery, J. P. (2000) · Biology of the Cell · doi:10.1016/s0248-4900(00)01101-1 · Cited by 392 · see citing works
“, 1999), and the serine/threonine phosphatase PP2A (Ito et al., 2000).”
BackgroundPP2A as a master regulator of the cell cycle
Wlodarchak, N., & Xing, Y. (2016) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2016.1143913 · Cited by 366 · see citing works
Physiological regulation of Akt activity and stability.
Liao, Y., & Hung, M. (2010) · PubMed Central · Cited by 343 · see citing works
Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins
Xing, Y., Xu, Y., Chen, Y., Jeffrey, P. D., Chao, Y., Lin, Z., Li, Z., Strack, S., Stock, J. B., & Shi, Y. (2006) · Cell · doi:10.1016/j.cell.2006.09.025 · Cited by 334 · see citing works
“In addition, an N-terminally truncated form of the B subunit PR61/B0g1 was found to be associated with a higher metastatic state of melanoma cells (Ito et al., 2000, 2003; Koma et al., 2004), whereas gain- and loss-of-function experiments established this regulatory subunit as a tumor suppressor…”
BackgroundInfluentialIdentification of specific PP2A complexes involved in human cell transformation
Chen, W., Possemato, R., Campbell, K. T., Plattner, C. A., Pallas, D. C., & Hahn, W. C. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00026-1 · Cited by 325 · see citing works
Protein phosphatase 2A: the Trojan Horse of cellular signaling
Sontag, E. (2001) · Cellular Signalling · doi:10.1016/s0898-6568(00)00123-6 · Cited by 328 · see citing works
All roads lead to <scp>PP</scp>2A: exploiting the therapeutic potential of this phosphatase
Sangodkar, J., Farrington, C. C., McClinch, K., Galsky, M. D., Kastrinsky, D. B., & Narla, G. (2016) · The FEBS Journal · doi:10.1111/febs.13573 · Cited by 312 · see citing works
Nayal, A., Webb, D. J., Brown, C. M., SCHAEFER, E. M., Vicente‐Manzanares, M., & Horwitz, A. R. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200509075 · Cited by 302 · see citing works
“Interestingly, paxillin interacts directly with the serine/threonine phosphatase PP2A (Ito et al., 2000), whose inhibition is observed in certain types of cancer and results in hyperphosphorylation of paxillin serine residues and dissolution of FAK–Src–paxillin complexes (Young et al., 2002; Romashko and Young, 2004).”
BackgroundTrockenbacher, A., Suckow, V., Foerster, J., Winter, J., Krauß, S., Ropers, H., Schneider, R., & Schweiger, S. (2001) · Nature Genetics · doi:10.1038/ng762 · Cited by 295 · see citing works
“and truncated forms of B-type regulatory subunits of PP2A promote cell motility through paxillin phosphorylatio”
BackgroundProtein Kinases and Phosphatases in the Control of Cell Fate
Bononi, A., Agnoletto, C., Marchi, E. D., Marchi, S., Patergnani, S., Bonora, M., Giorgi, C., Missiroli, S., Poletti, F., Rimessi, A., et al. (2011) · Enzyme Research · doi:10.4061/2011/329098 · Cited by 283 · see citing works
“Although most regulatory subunits do not contain obvious targeting motifs, their presence certainly influences the compartmentalization of PP2a, such as focal adhesions [147] and the microtubule cytoskeleton [142].”
BackgroundPP2A mRNA Expression Is Quantitatively Decreased in Alzheimer's Disease Hippocampus
Vogelsberg-Ragaglia, V., Schuck, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7630 · Cited by 281 · see citing works
Protein kinase A activates protein phosphatase 2A by phosphorylation of the B56δ subunit
Ahn, J., McAvoy, T., Rakhilin, S., Nishi, A., Greengard, P., & Nairn, A. C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611532104 · Cited by 265 · see citing works
Arnold, H. K., & Sears, R. C. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.7.2832-2844.2006 · Cited by 251 · see citing works
“An N-terminal deletion mutant of B56 1, found in a mouse melanoma cell line, has been shown to result in increased metastasis by deregulation of paxillin (23) and inhibition of the gamma irradiation cell cycle check point, contributing to genomic instability (23, 24).”
BackgroundInvolvement of PP2A in viral and cellular transformation
Arroyo, J. D., & Hahn, W. C. (2005) · Oncogene · doi:10.1038/sj.onc.1209038 · Cited by 237 · see citing works
“In addition, a truncated B56g1 isoform is expressed in a metastatic clone, BL6, of mouse B16 melanoma cells (Ito et al., 2000).”
BackgroundLetourneux, C., Rocher, G., & Porteu, F. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600980 · Cited by 224 · see citing works
“Indeed, decreased B56g expression or activity are involved in SV40 small t tumoral activities (Chen et al, 2004) and melanoma metastasis progression (Ito et al, 2000).”
BackgroundA role for heterologous gap junctions between melanoma and endothelial cells in metastasis
Ito, A., Katoh, F., Kataoka, T. R., Okada, M., Tsubota, N., Asada, H., Yoshikawa, K., Maeda, S., Kitamura, Y., Yamasaki, H., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8257 · Cited by 194 · see citing works
“Application of this method to F10 and BL6 cells yielded a set of genes that were transcriptionally upregulated in BL6 cells (5, 6).”
MethodSelf-citationRole of serine/threonine protein phosphatase 2A in cancer
Schönthal, A. H. (2001) · Cancer Letters · doi:10.1016/s0304-3835(01)00561-4 · Cited by 186 · see citing works
Ivaska, J., Nissinen, L. M., Immonen, N., Eriksson, J., Kähäri, V., & Heino, J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.5.1352-1359.2002 · Cited by 176 · see citing works
Regulation and Function of Protein Kinases and Phosphatases
Cheng, H.-C., Qi, R., Paudel, H., & Zhu, H.-J. (2011) · Enzyme Research · doi:10.4061/2011/794089 · Cited by 147 · see citing works
West, K. A., Zhang, H., Brown, M. C., et al. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200101039 · Cited by 163 · see citing works
“Paxillin, and its tyrosine phosphorylation, has been implicated in the regulation of cell migration (Liu et al., 1999; Riedy et al., 1999; Salgia et al., 1999; Turner et al., 1999; Ito et al., 2000; Nakamura et al., 2000; Petit et al., 2000; Yano et al., 2000).”
BackgroundRuvolo, P. P. (2016) · BBA Clinical · doi:10.1016/j.bbacli.2016.08.002 · Cited by 143 · see citing works
α4 integrins and the immune response
Rose, D. M., Han, J., & Ginsberg, M. H. (2002) · Immunological Reviews · doi:10.1034/j.1600-065x.2002.18611.x · Cited by 143 · see citing works
Structure, Regulation, and Pharmacological Modulation of PP2A Phosphatases
Lambrecht, C., Haesen, D., Sents, W., Ivanova, E., & Janssens, V. (2013) · Methods in Molecular Biology · doi:10.1007/978-1-62703-562-0_17 · Cited by 140 · see citing works
Phosphatases in cell–matrix adhesion and migration
Larsen, M., Tremblay, M. L., & Yamada, K. M. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1199 · Cited by 143 · see citing works
Protein phosphatase 2A regulatory subunits and cancer
Eichhorn, P. J. A., Creyghton, M. P., & Bernards, R. (2009) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2008.05.005 · Cited by 513 · see citing works
Ishii, T., Onda, H., Tanigawa, A., et al. (2005) · DNA Research · doi:10.1093/dnares/dsi020 · Cited by 140 · see citing works
Self-citationKim, K.-Y., Baek, A., Hwang, J.-E., Choi, Y. A., Jeong, J., Lee, M.-S., Cho, D. H., Lim, J., Kim, K. I., & Yang, Y. D. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2641 · Cited by 135 · see citing works
Kanegan, M. J. V., Adams, D. G., Wadzinski, B. E., & Strack, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506986200 · Cited by 132 · see citing works
Planar cell polarization requires Widerborst, a B′ regulatory subunit of protein phosphatase 2A
Hannus, M., Feiguin, F. M., Heisenberg, C., & Eaton, S. (2002) · Development · doi:10.1242/dev.129.14.3493 · Cited by 130 · see citing works
Watabe, K., Ito, A., Asada, H., et al. (2001) · Japanese Journal of Cancer Research · doi:10.1111/j.1349-7006.2001.tb01076.x · Cited by 126 · see citing works
Self-citationStructural Basis of PP2A Inhibition by Small t Antigen
Cho, U., Morrone, S. R., Sablina, A. A., Arroyo, J. D., Hahn, W. C., & Xu, W. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050202 · Cited by 124 · see citing works
Regulation of Focal Adhesion Kinase by a Novel Protein Inhibitor FIP200
Abbi, S., Ueda, H. R., Zheng, C., Cooper, L. A., Zhao, J., Christopher, R. A., & Guan, J. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-05-0295 · Cited by 120 · see citing works
“Also, the phosphatase PP2A that dephosphorylates paxillin negatively regulates cell cycle progression and cell motility (Wera and Hemmings, 1995; Ito et al., 2000).”
BackgroundIto, A., Jippo, T., Wakayama, T., Morii, E., Koma, Y.-I., Onda, H., Nojima, H., Iseki, S., & Kitamura, Y. (2003) · Blood · doi:10.1182/blood-2002-07-2265 · Cited by 119 · see citing works
Self-citationProtein phosphatase 2A (PP2A), a drugable tumor suppressor in Ph1(+) leukemias
Perrotti, D., & Neviani, P. (2008) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9119-x · Cited by 113 · see citing works
“The B subunit B56γ (of the PR61/B′ family) has been found overexpressed in metastatic melanoma cells compared to normal melanocytes [45]; in these cells, PP2A failed to dephosphorylate the protein paxillin in focal adhesions, therefore enhancing the invasiveness of metastatic clones [46].”
BackgroundArnold, H. K., & Sears, R. C. (2008) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9128-9 · Cited by 111 · see citing works
“In addition, a truncated form of B56γ1, called ΔB56γ1, was identified in a mouse melanoma cell line that demonstrated increased metastatic potential [28].”
BackgroundRuediger, R., Ruiz, J., & Walter, G. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05744-11 · Cited by 98 · see citing works
PP2A-B′ holoenzyme substrate recognition, regulation and role in cytokinesis
Wu, C.-G., Chen, H., Guo, F., Yadav, V. K., Mcilwain, S. J., Rowse, M., Choudhary, A., Lin, Z., Li, Y., Gu, T., et al. (2017) · Cell Discovery · doi:10.1038/celldisc.2017.27 · Cited by 85 · see citing works
Meeusen, B., & Janssens, V. (2018) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.10.002 · Cited by 96 · see citing works
“Expression of PPP2R5C was specifically decreased in primary melanomas as opposed to pre-malignant melanocytic naevi (63), potentially related to a role of B56γ in paxillin dephosphorylation at focal adhesions (87).”
ResultJanssens, V., & Rebollo, A. (2012) · Current Molecular Medicine · doi:10.2174/156652412799218930 · Cited by 93 · see citing works
“Interestingly, metastatic melanoma cells expressing a cancerassociated truncation mutant of PR61/B’ [68] show significantly less irradiation-induced Mdm2 phosphorylation, resulting in decreased apoptosis and thus increased radioresistance [69].”
BackgroundDeterminants for Substrate Specificity of Protein Phosphatase 2A
Slupe, A. M., Merrill, R. A., & Strack, S. (2011) · Enzyme Research · doi:10.4061/2011/398751 · Cited by 91 · see citing works
“Further, PP2A functions as a critical tumor suppressor whose interruption leads to proliferative diseases [14].”
BackgroundLi, X., & Virshup, D. M. (2002) · European Journal of Biochemistry · doi:10.1046/j.0014-2956.2001.02680.x · Cited by 83 · see citing works
Glycogen synthase kinase 3 in the world of cell migration
Sun, T., Rodriguez, M., & Kim, L. (2009) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.2009.01141.x · Cited by 80 · see citing works
“It is worth mentioning that protein phosphatase 2A (PP2A) ⁄ B56 complex, often envisioned as a GSK3 antagonist, also regulates cell motility by dephosphorylating paxillin (Ito et al. 2000).”
BackgroundFocal adhesion kinase: protein interactions and cellular functions.
Abbi, S., & Guan, J. (2002) · PubMed · doi:10.14670/hh-17.1163 · Cited by 80 · see citing works
Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation
Chastney, M. R., Lawless, C., Humphries, J. D., Warwood, S., Jones, M., Knight, D., Jørgensen, C., & Humphries, M. J. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.202003038 · Cited by 78 · see citing works
Dong, J., Lau, L.-S., Ng, Y., et al. (2008) · Biochemical Journal · doi:10.1042/bj20080170 · Cited by 77 · see citing works
Protein phosphatase 2A – structure, function and role in neurodevelopmental disorders
Sandal, P., Jong, C. J., Merrill, R. A., Song, J., & Strack, S. (2021) · Journal of Cell Science · doi:10.1242/jcs.248187 · Cited by 72 · see citing works
Sequential Phosphorylation of Smoothened Transduces Graded Hedgehog Signaling
Su, Y., Ospina, J. K., Zhang, J., Michelson, A. P., Schoen, A. M., & Zhu, A. J. (2011) · Science Signaling · doi:10.1126/scisignal.2001747 · Cited by 73 · see citing works
The MID1/PP2A complex: a key to the pathogenesis of Opitz BBB/G syndrome
Schweiger, S., & Schneider, R. (2003) · BioEssays · doi:10.1002/bies.10256 · Cited by 72 · see citing works
Shtrichman, R., Sharf, R., & Kleinberger, T. (2000) · Oncogene · doi:10.1038/sj.onc.1203705 · Cited by 68 · see citing works
“In another cell type, B'g1 was reported to target PP2A to focal adhesions (Ito et al., 2000).”
BackgroundThe focal adhesion protein paxillin regulates contraction in canine tracheal smooth muscle
Tang, D. D., Wu, M., Saez, A. M. O., et al. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.021006 · Cited by 66 · see citing works
“Paxillin has been implicated in the regulation of cytoskeletal dynamics in a number of cell types (Turner et al. 1999; Ito et al. 2000; Nakamura et al. 2000; Petit et al. 2000; West et al. 2001).”
BackgroundProtein phosphatase 2A as therapeutic targets in various disease models
Baskaran, R., & Velmurugan, B. K. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.08.063 · Cited by 62 · see citing works
Interaction of Paxillin with p21-activated Kinase (PAK)
Hashimoto, S., Tsubouchi, A., Mazaki, Y., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m005854200 · Cited by 61 · see citing works
Self-citationMartens, E., Stevens, I., Janssens, V., Vermeesch, J., Götz, J., Goris, J., & Van Hoof, C. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.12.047 · Cited by 57 · see citing works
Sontag, J. M., & Sontag, E. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6300-7 · Cited by 57 · see citing works
PP2A-Mediated Anticancer Therapy
Chen, W., Wang, Z., Jiang, C., & Ding, Y. (2013) · Gastroenterology Research and Practice · doi:10.1155/2013/675429 · Cited by 57 · see citing works
“This review focuses on PP2A structure, cancer-associated mutations, and the targeting of PP2A-related molecules to restore or reactivate PP2A in anticancer therapy, especially in digestive system cancer therapy.”
BackgroundVereshchagina, N., Ramel, M., Bitoun, E., & WILSON, C. G. (2008) · Journal of Cell Science · doi:10.1242/jcs.035220 · Cited by 57 · see citing works
“Reduced PP2A-B γ activity has also been linked to the establishment and progression of melanomas (Deichmann et al., 2001; Ito et al., 2000; Ito et al., 2003a; Ito et al., 2003b).”
BackgroundBhardwaj, A., Singh, S., Srivastava, S. K., Arora, S., Hyde, S. J., Andrews, J., Grizzle, W. E., & Singh, A. P. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.141 · Cited by 56 · see citing works
“A similar role of PP2A in the regulation of malignant behaviour and EMT has been reported in other cancer types as well (Ito et al, 2000; Xu and Deng, 2006).”
BackgroundInvolvement of phosphorylation of tyr‐31 and tyr‐118 of paxillin in MM1 cancer cell migration
Iwasaki, T., Nakata, A., Mukai, M., et al. (2001) · International Journal of Cancer · doi:10.1002/ijc.1609 · Cited by 52 · see citing works
Self-citationSaraf, A., Oberg, E. A., & Strack, S. (2010) · Biochemistry · doi:10.1021/bi902160t · Cited by 45 · see citing works
“The divergent N- and C-terminal regions may be largely unstructured and have been implicated in subcellular targeting (18,19).”
BackgroundKong, M., Bui, T. V., Ditsworth, D., Gruber, J. J., Goncharov, D., Krymskaya, V. P., Lindsten, T., & Thompson, C. B. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703159200 · Cited by 43 · see citing works
Saraf, A., Virshup, D. M., & Strack, S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607407200 · Cited by 43 · see citing works
Guo, C. Y., Brautigan, D. L., & Larner, J. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110092200 · Cited by 43 · see citing works
Lee, T.-Y., Lai, T.-Y., Lin, S.-C., Wu, C.-W., Ni, I.-F., Yang, Y.-S., Hung, L., Law, B. K., & Chiang, C.-W. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.094953 · Cited by 41 · see citing works
B56 Regulatory Subunit of Protein Phosphatase 2A Mediates Valproic Acid-Induced p300 Degradation
Chen, J., St‐Germain, J. R., & Li, Q. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.2.525-532.2005 · Cited by 41 · see citing works
“cell growth, apoptosis, and neoplastic progression (16, 28).”
BackgroundGau, D. M., Lesnock, J. L., Hood, B. L., Bhargava, R., Sun, M., Darcy, K. M., Luthra, S., Chandran, U. R., Conrads, T. P., Edwards, R. P., et al. (2015) · Cell Cycle · doi:10.1080/15384101.2015.1036203 · Cited by 40 · see citing works
Paxillin: A Hub for Mechano-Transduction from the β3 Integrin-Talin-Kindlin Axis
Ripamonti, M., Wehrle‐Haller, B., & de Curtis, I. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.852016 · Cited by 40 · see citing works
Pandey, P., Seshacharyulu, P., Das, S., Rachagani, S., Ponnusamy, M. P., Yan, Y., Johansson, S. L., Datta, K., Lin, M. F., & Batra, S. K. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.160 · Cited by 39 · see citing works
G1 and S-Phase Checkpoints, Chromosome Instability, and Cancer
Nojima, H. (2004) · Humana Press eBooks · doi:10.1385/1-59259-788-2:003 · Cited by 39 · see citing works
Self-citationMiura, D., Kida, Y., & Nojima, H. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.04.080 · Cited by 39 · see citing works
Self-citationOgura, K., Okada, T., Mitani, S., Gengyo‐Ando, K., Baillie, D. L., Kohara, Y., & Goshima, Y. (2010) · Development · doi:10.1242/dev.050708 · Cited by 39 · see citing works
Eto, M., Kirkbride, J. A., Elliott, E. A., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700944200 · Cited by 38 · see citing works
Young, M. R., Kolesiak, K., & Meisinger, J. (2002) · International Journal of Cancer · doi:10.1002/ijc.10491 · Cited by 38 · see citing works
Hagiyama, M., Ichiyanagi, N., Kimura, K. B., Murakami, Y., & Ito, A. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080743 · Cited by 36 · see citing works
“The procedure for immunoprecipitation with RP6 was essentially similar to that described previously.(27) To use 3E1 for immunoprecipitation, 100 g of the 3E1 antibody were crosslinked with 100 l of the affinity-purified goat anti-IgY antibody-conjugated Microbeads (2 mg IgG/ml Microbeads, 50% slurry in Tris-buffered s…”
MethodSelf-citationA B56 regulatory subunit of protein phosphatase 2A localizes to nuclear speckles in cardiomyocytes
Gigena, M. S., Ito, A., Nojima, H., & Rogers, T. B. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01291.2004 · Cited by 34 · see citing works
“The production and purification of polyclonal anti-B56 was previously described (12).”
BackgroundInfluentialSelf-citationIncreased Expression of a Nucleolar Nop5/Sik Family Member in Metastatic Melanoma Cells
Nakamoto, K., Ito, A., Watabe, K., Koma, Y., Asada, H., Yoshikawa, K., Shinomura, Y., Matsuzawa, Y., Nojima, H., & Kitamura, Y. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62523-0 · Cited by 32 · see citing works
“The method for constructing a subtracted cDNA library has been described previously.(19,21,35) After four rounds of subtraction, 1400 clones were rescued and subjected to Northern blot analysis with the RNA of F10 and BL6 cells.”
MethodSelf-citationModulation of Thr Phosphorylation of Integrin β1 during Muscle Differentiation
Kim, S., Kwon, M. S., Park, C. S., Choi, K.-R., Chun, J., Ahn, J., & Song, W. K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311581200 · Cited by 32 · see citing works
Sato, J., Shimizu, H., Kasama, T., Yabuta, N., & Nojima, H. (2009) · Genes to Cells · doi:10.1111/j.1365-2443.2009.01296.x · Cited by 27 · see citing works
“Of relevance to this paper is the B′α (alternatively called B56gamma) subunit subfamily, which includes three alternative splicing variants with differing subcellular localizations (Ito et al. 2000), namely, either in the nucleus (B′α1 and B′α2) or in the cytoplasm (B′α3).”
BackgroundMethodInfluentialSelf-citationDeichmann, M., Polychronidis, M., Wacker, J., Thome, M., & Näher, H. (2001) · Melanoma Research · doi:10.1097/00008390-200112000-00004 · Cited by 30 · see citing works
Paxillin phosphorylation at serine 273 and its effects on Rac, Rho and adhesion dynamics
Tang, K., Boudreau, C. G., Brown, C. M., et al. (2018) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006303 · Cited by 30 · see citing works
A derivative of oleamide potently inhibits the spontaneous metastasis of mouse melanoma BL6 cells
Ito, A. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh208 · Cited by 30 · see citing works
Self-citationFunctional importance of PP2A regulatory subunit loss in breast cancer
Watt, L. F., Panicker, N., Mannan, A., Copeland, B., Kahl, R. G. S., Dun, M. D., Young, B., Roselli, S., & Verrills, N. M. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4403-5 · Cited by 29 · see citing works
Liang, Z., Ge, X., Xu, M., Qin, H., Wu, M., Shen, M., Zhang, Y., Liu, X., Chen, K., Li, W., et al. (2021) · Cancer Science · doi:10.1111/cas.14863 · Cited by 29 · see citing works
Silverstein, A. M., Davis, A. J., Bielinski, V. A., Esplin, E. D., Mahmood, N. A., & Mumby, M. C. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00168-6 · Cited by 28 · see citing works
Ravi, A., Kaushik, S., Ravichandran, A., Pan, C. Q., & Low, B. C. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.616839 · Cited by 27 · see citing works
“Various processes modulate the functions of DLC1: phosphorylation by Akt (36), interactions with FAK and the tensin family proteins targeting it to FAs (17, 20, 37), its dimerization (38), or masking by other protein partners (24, 39).”
BackgroundInfluentialJanssens, V., Zwaenepoel, K., Rossé, C., Petit, M. M. R., Goris, J., & Parker, P. J. (2016) · Journal of Cell Science · doi:10.1242/jcs.175778 · Cited by 27 · see citing works
“Earlier work has already demonstrated a role for a specific PP2A-B′γ1 complex in regulating paxillin dephosphorylation at focal adhesions (Ito et al., 2000) – further underscoring the importance of localised regulation of protein dephosphorylation at sites of cell–substratum contacts – as well as…”
BackgroundBerrou, E., & Bryckaert, M. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.12.002 · Cited by 26 · see citing works
Ito, A., Koma, Y.-I., Watabe, K., Nagano, T., Endo, Y., Nojima, H., & Kitamura, Y. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63800-x · Cited by 24 · see citing works
“Our previous work showed that 1 prevents the B56 1-containing PP2A heterotrimer from dephosphorylating its specific substrates.(15) Consistent with this inhibitory effect of 1, NIH3T3 cells that stably express 1 are defective in cell-cycle checkpoint regulation when exposed to -radiation.”
BackgroundMethodResultInfluentialSelf-citationGilan, O., Diesch, J., Amalia, M., Jastrzebski, K., Chüeh, A. C., Verrills, N. M., Pearson, R. B., Mariadason, J. M., Tulchinsky, E. M., Hannan, R. D., et al. (2014) · Oncogene · doi:10.1038/onc.2014.26 · Cited by 24 · see citing works
Tabara, H., Naito, Y., Ito, A., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026034 · Cited by 24 · see citing works
“Moreover, both GAK and its association partner clathrin heavy chain (CHC), localize to both the cytoplasm and nucleus with distinct association modes, and CHC colocalizes with GAK in the nucleus, while Cyclin G and PP2A B’c are also present in the nucleus [17], [20], [21].”
BackgroundSelf-citationChe, L., Wu, J., Xu, C.-Y., Cai, Y., Lin, J., Du, Z., Shi, J., Han, T., He, Y.-Q., Lin, Y., et al. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115132 · Cited by 23 · see citing works
Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma IDH Wildtype
Kashani, E., & Vassella, E. (2022) · Cancers · doi:10.3390/cancers14215227 · Cited by 22 · see citing works
“Sustained p-ATM activity can trigger phosphorylation of PPP2R5C complexes at Ser510, leading to PPP2R5Ccontaining PP2A complex formation, which contributes to p53 activation [128,132].”
BackgroundInfluential
- Authors
- Ito, A., Kataoka, T. R., Watanabe, M., Nishiyama, K., Mazaki, Y., Sabe, H., Kitamura, Y., & Nojima, H.
- Affiliations
- Medical & Biological Laboratories (Japan) (JP)
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Kyoto University (JP)
- Corresponding author
- Nojima, Hiroshi
- Venue
- The EMBO Journal
- Published
- 2000-02-15
- Volume
- 19
- Issue
- 4
- Pages
- 562-571
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC305594
- OpenAlex
- W2062708599
- Cited by
- 159
- References
- 40
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 11 · 2014: 4 · 2013: 8 · 2012: 5
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- protein phosphatase 2A, protein phosphatase 2A regulatory subunit, truncated protein isoform, paxillin phosphorylation, cell motility, metastasis, melanoma, focal adhesions, retrotransposon insertion, actin cytoskeleton, cell spreading, malignant progression
- MeSH terms
- Animals, Base Sequence, Cell Cycle, Cell Movement, Cytoskeletal Proteins, Cytoskeleton, Melanoma, Experimental, Molecular Sequence Data, Phosphoprotein Phosphatases, Phosphoproteins, Phosphorylation, RNA, Messenger, RNA, Neoplasm, Serine, Tumor Cells, Cultured, Gene Expression, 3T3 Cells, DNA Primers, COS Cells, Protein Structure, Quaternary, Mice, Paxillin
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