Transformation of Mammalian Cells by Constitutively Active MAP Kinase Kinase

Mansour, Sam J., Matten, Wayne T., Hermann, April S., Candia, Julian M., Rong, Sing, Fukasawa, Kenji, Vande Woude, George F., Ahn, Natalie G.·1994·Science

DOI 10.1126/science.8052857

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Abstract

Mitogen-activated protein (MAP) kinase kinase (MAPKK) activates MAP kinase in a signal transduction pathway that mediates cellular responses to growth and differentiation factors. Oncogenes such as ras , src , raf , and mos have been proposed to transform cells by prolonging the activated state of MAPKK and of components downstream in the signaling pathway. To test this hypothesis, constitutively active MAPKK mutants were designed that had basal activities up to 400 times greater than that of the unphosphorylated wild-type kinase. Expression of these mutants in mammalian cells activated AP-1-regulated transcription. The cells formed transformed foci, grew efficiently in soft agar, and were highly tumorigenic in nude mice. These findings indicate that constitutive activation of MAPKK is sufficient to promote cell transformation.

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Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation
Marshall, C. J. (1995) · Cell · doi:10.1016/0092-8674(95)90401-8 · Cited by 3,906
Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways
Whitmarsh, A. J., & Davis, R. J. (1996) · Journal of Molecular Medicine · doi:10.1007/s001090050063 · Cited by 1,543
The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway
Coso, O. A., Chiariello, M., Yu, J.-C., Teramoto, H., Crespo, P., Xu, N., Miki, T., & Silvio Gutkind, J. (1995) · Cell · doi:10.1016/s0092-8674(05)80018-2 · Cited by 1,397
Phosphorylation and Functional Inactivation of TSC2 by Erk
Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., & Pandolfi, P. P. (2005) · Cell · doi:10.1016/j.cell.2005.02.031 · Cited by 1,268
Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling
Lin, A. W., Barradas, M., Stone, J. C., van Aelst, L., Serrano, M., & Lowe, S. W. (1998) · Genes & Development · doi:10.1101/gad.12.19.3008 · Cited by 945
Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies
Bahar, M. E., Kim, H. J., & Kim, D. R. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01705-z · Cited by 888
Translational Control by MAPK Signaling in Long-Term Synaptic Plasticity and Memory
Kelleher, R. J., Govindarajan, A., Jung, H.-Y., Kang, H., & Tonegawa, S. (2004) · Cell · doi:10.1016/s0092-8674(04)00115-1 · Cited by 845
The Pathways Connecting G Protein-coupled Receptors to the Nucleus through Divergent Mitogen-activated Protein Kinase Cascades
Gutkind, J. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.4.1839 · Cited by 812
Activation mechanism of the MAP kinase ERK2 by dual phosphorylation
Canagarajah, B. J., Khokhlatchev, A., Cobb, M. H., & Goldsmith, E. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80351-7 · Cited by 729
Mapk signal specificity: The right place at the right time
Murphy, L. O., & Blenis, J. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.03.009 · Cited by 707
Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation
Khosravi-Far, R., Solski, P. A., Clark, G. J., Kinch, M. S., & Der, C. J. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.11.6443 · Cited by 683
Multicenter Phase II Study of the Oral MEK Inhibitor, CI-1040, in Patients With Advanced Non-Small-Cell Lung, Breast, Colon, and Pancreatic Cancer
Rinehart, J., Adjei, A. A., LoRusso, P. M., Waterhouse, D., Hecht, J. R., Natale, R. B., Hamid, O., Varterasian, M., Asbury, P., Kaldjian, E. P., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.01.185 · Cited by 645
MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road
Caunt, C. J., Sale, M. J., Smith, P. D., & Cook, S. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc4000 · Cited by 606
Assembly of cyclin D-dependent kinase and titration of p27 Kip1 regulated by mitogen-activated protein kinase kinase (MEK1)
Cheng, M., Sexl, V., Sherr, C. J., & Roussel, M. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.3.1091 · Cited by 496
MEK inhibitors: The chemistry and biological activity of U0126, its analogs, and cyclization products
Duncia, J. V., Santella, J. B., Higley, C. A., Pitts, W. J., Wityak, J., Frietze, W. E., Rankin, F. W., Sun, J.-H., Earl, R. A., Tabaka, A. C., et al. (1998) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(98)00522-8 · Cited by 401
MAPK Signaling Up-regulates the Activity of Hypoxia-inducible Factors by Its Effects on p300
Sang, N., Stiehl, D. P., Bohensky, J., Leshchinsky, I., Srinivas, V., & Caro, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209702200 · Cited by 370
Activation of Signalling by the Activin Receptor Complex
Attisano, L., Wrana, J. L., Montalvo, E., & Massagué, J. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.3.1066 · Cited by 316
Cellular Transformation and Malignancy Induced by ras Require c-jun
Johnson, R., Spiegelman, B., Hanahan, D., & Wisdom, R. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.8.4504 · Cited by 282
The structure of mitogen-activated protein kinase p38 at 2.1-Å resolution
Wang, Z., Harkins, P. C., Ulevitch, R. J., Han, J., Cobb, M. H., & Goldsmith, E. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2327 · Cited by 275
Mitogen-activated protein kinase regulates dopamine transporter surface expression and dopamine transport capacity
Morón, J. A., Zakharova, I., Ferrer, J. V., Merrill, G. A., Hope, B., Lafer, E. M., Lin, Z. C., Wang, J. B., Javitch, J. A., Galli, A., et al. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-24-08480.2003 · Cited by 262
Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors
Yang, S.-H., Galanis, A., & Sharrocks, A. D. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.6.4028 · Cited by 244
HER‐2/ neu Signal Transduction in Human Breast and Ovarian Cancer
Reese, D. M., & Slamon, D. J. (1997) · STEM CELLS · doi:10.1002/stem.150001 · Cited by 229
Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism
Yuen, E. Y. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1187-05.2005 · Cited by 225
Serine Phosphorylation and Negative Regulation of Stat3 by JNK
Lim, C. P., & Cao, X. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.43.31055 · Cited by 225
Requirement of activation of JNK and p38 for environmental stress-induced erythroid differentiation and apoptosis and of inhibition of ERK for apoptosis
Nagata, Y., & Todokoro, K. (1999) · Blood · doi:10.1182/blood.v94.3.853.415a12_853_863 · Cited by 218
Differential Regulation of Mitogen-Activated Protein Kinases ERK1/2 and ERK5 by Neurotrophins, Neuronal Activity, and cAMP in Neurons
Cavanaugh, J. E., Ham, J., Hetman, M., Poser, S., Yan, C., & Xia, Z. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00434.2001 · Cited by 196
Chronic activation of ERK and neurodegenerative diseases
Colucci‐D'Amato, L., Perrone‐Capano, C., & di Porzio, U. (2003) · BioEssays · doi:10.1002/bies.10355 · Cited by 195
An ERK2 docking site in the Pointed domain distinguishes a subset of ETS transcription factors
Seidel, J. J., & Graves, B. J. (2002) · Genes & Development · doi:10.1101/gad.950902 · Cited by 182
Sustained activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway is required for megakaryocytic differentiation of K562 cells
Racke, F. K., Lewandowska, K., Goueli, S., & Goldfarb, A. N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.37.23366 · Cited by 182
Untitled work
(2001) · PubMed · Cited by 170
Reduction in the requirement of oncogenic Ras signaling to activation of PI3K/AKT pathway during tumor maintenance
Lim, K.-H., & Counter, C. M. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.10.014 · Cited by 159
Extracellular Signal-Regulated Kinase–Dependent Stabilization of Hepatic Low-Density Lipoprotein Receptor mRNA by Herbal Medicine Berberine
Abidi, P., Zhou, Y., Jiang, J.-D., & Liu, J. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000181761.16341.2b · Cited by 152
Reactive Oxygen-induced Carcinogenesis Causes Hypermethylation of p16Ink4a and Activation of MAP Kinase
Govindarajan, B., Klafter, R., Miller, M. S., Mansur, C., Mizesko, M., Bai, X., LaMontagne, K., & Arbiser, J. L. (2002) · Molecular Medicine · doi:10.1007/bf03401997 · Cited by 145
Bortezomib represses HIF-1α protein expression and nuclear accumulation by inhibiting both PI3K/Akt/TOR and MAPK pathways in prostate cancer cells
Befani, C. D., Vlachostergios, P. J., Hatzidaki, E., Patrikidou, A., Bonanou, S., Simos, G., Papandreou, C. N., & Liakos, P. (2012) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0805-8 · Cited by 135
The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf
Li, W., Han, M., & Guan, K.-L. (2000) · Genes & Development · doi:10.1101/gad.14.8.895 · Cited by 129
Activation of ERK1/2 MAP kinase pathway induces tight junction disruption in human corneal epithelial cells
Wang, Y., Zhang, J., Yi, X.-J., & Yu, F.-S. X. (2004) · Experimental Eye Research · doi:10.1016/j.exer.2003.09.002 · Cited by 122
Untitled work
(2001) · PubMed · Cited by 120
M-Ras/R-Ras3, a Transforming Ras Protein Regulated by Sos1, GRF1, and p120 Ras GTPase-activating Protein, Interacts with the Putative Ras Effector AF6
Quilliam, L. A., Castro, A. F., Rogers-Graham, K. S., Martin, C. B., Der, C. J., & Bi, C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.34.23850 · Cited by 119
Tumor Necrosis Factor-α Induces Interleukin-6 Production and Integrin Ligand Expression by Distinct Transduction Pathways
De Cesaris, P., Starace, D., Riccioli, A., Padula, F., Filippini, A., & Ziparo, E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.13.7566 · Cited by 116
The JNKK2-JNK1 fusion protein acts as a constitutively active c-Jun kinase that stimulates c-Jun transcription activity
Zheng, C., Xiang, J., Hunter, T., & Lin, A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.41.28966 · Cited by 110
ERK1/2 Antagonizes Glycogen Synthase Kinase-3β-induced Apoptosis in Cortical Neurons
Hetman, M., Hsuan, S.-L., Habas, A., Higgins, M. J., & Xia, Z. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111227200 · Cited by 88
Induced Expression of Rnd3 Is Associated with Transformation of Polarized Epithelial Cells by the Raf–MEK–Extracellular Signal-Regulated Kinase Pathway
Hansen, S. H., Zegers, M. M. P., Woodrow, M., Rodriguez-Viciana, P., Chardin, P., Mostov, K. E., & McMahon, M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.24.9364-9375.2000 · Cited by 85
Brain-derived neurotrophic factor induces matrix metalloproteinase 9 expression in neurons via the serum response factor/c-Fos pathway
Kuzniewska, B., Rejmak, E., Malik, A. R., Jaworski, J., Kaczmarek, L., & Kalita, K. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00008-13 · Cited by 82
Role for DUSP1 (dual-specificity protein phosphatase 1) in the regulation of autophagy
Wang, J., Zhou, J.-Y., Kho, D., Reiners, J. J., & Wu, G. S. (2016) · Autophagy · doi:10.1080/15548627.2016.1203483 · Cited by 82
Phosphorylation acts positively and negatively to regulate MRTF-A subcellular localisation and activity
Panayiotou, R., Miralles, F., Pawlowski, R., Diring, J., Flynn, H. R., Skehel, M., & Treisman, R. (2016) · eLife · doi:10.7554/elife.15460 · Cited by 79
Cytokine-induced myeloid differentiation is dependent on activation of the MEK/ERK pathway
Miranda, M. B., Xu, H., Torchia, J. A., & Johnson, D. E. (2005) · Leukemia Research · doi:10.1016/j.leukres.2005.03.016 · Cited by 62
Effect of human papillomavirus type 16 oncogenes on MAP kinase activity
Gu, Z., & Matlashewski, G. (1995) · Journal of Virology · doi:10.1128/jvi.69.12.8051-8056.1995 · Cited by 62
Specific Interaction of Egr1 and c/EBPβ Leads to the Transcriptional Activation of the Human Low Density Lipoprotein Receptor Gene
Zhang, F., Lin, M., Abidi, P., Thiel, G., & Liu, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305564200 · Cited by 60
Phase 1 study of the pan-HER inhibitor dacomitinib plus the MEK1/2 inhibitor PD-0325901 in patients with KRAS-mutation-positive colorectal, non-small-cell lung and pancreatic cancer
van Geel, R. M. J. M., van Brummelen, E. M. J., Eskens, F. A. L. M., Huijberts, S. C. F. A., de Vos, F. Y. F. L., Lolkema, M. P. J. K., Devriese, L. A., Opdam, F. L., Marchetti, S., Steeghs, N., et al. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0776-z · Cited by 55
Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation
Mathiasen, D. P., Egebjerg, C., Andersen, S. H., Rafn, B., Puustinen, P., Khanna, A., Daugaard, M., Valo, E., Tuomela, S., Bøttzauw, T., et al. (2012) · Oncogene · doi:10.1038/onc.2011.230 · Cited by 44
Abrogation of nerve growth factor-induced terminal differentiation by ret oncogene involves perturbation of nuclear translocation of ERK
Colucci-D'Amato, G. L., D'Alessio, A., Califano, D., Calı̀, G., Rizzo, C., Nitsch, L., Santelli, G., & de Franciscis, V. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.25.19306 · Cited by 37

Authors: Mansour, S. J., Matten, W. T., Hermann, A. S., Candia, J. M., Rong, S., Fukasawa, K., Vande Woude, G. F., & Ahn, N. G.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1994-08-12
Volume: 265
Issue: 5174
Pages: 966-970
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.8052857
OpenAlex: W2001521752
Cited by: 1,353
References: 0
FWCI: 30.52
Type: journal article
Language: en
Open access: closed

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Transformation of Mammalian Cells by Constitutively Active MAP Kinase Kinase

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