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Science 12 August 1994:
Vol. 265. no. 5174, pp. 966 - 970
DOI: 10.1126/science.8052857
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Articles

Science, Vol 265, Issue 5174, 966-970
Copyright © 1994 by American Association for the Advancement of Science

articles

Transformation of mammalian cells by constitutively active MAP kinase kinase

SJ Mansour, WT Matten, AS Hermann, JM Candia, S Rong, K Fukasawa, GF Vande Woude, and NG Ahn

Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309.

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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E. Y. Yuen, Q. Jiang, P. Chen, Z. Gu, J. Feng, and Z. Yan (2005)
J. Neurosci. 25, 5488-5501
   Abstract »    Full Text »    PDF »
Odorant-Induced Activation of Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase in the Olfactory Bulb Promotes Survival of Newly Formed Granule Cells.
N. Miwa and D. R. Storm (2005)
J. Neurosci. 25, 5404-5412
   Abstract »    Full Text »    PDF »
Regulation of NMDA Receptors by Neuregulin Signaling in Prefrontal Cortex.
Z. Gu, Q. Jiang, A. K. Y. Fu, N. Y. Ip, and Z. Yan (2005)
J. Neurosci. 25, 4974-4984
   Abstract »    Full Text »    PDF »
A genetically defined mouse ovarian carcinoma model for the molecular characterization of pathway-targeted therapy and tumor resistance.
D. Xing and S. Orsulic (2005)
PNAS 102, 6936-6941
   Abstract »    Full Text »    PDF »
Nongenotropic, Anti-Apoptotic Signaling of 1{alpha},25(OH)2-Vitamin D3 and Analogs through the Ligand Binding Domain of the Vitamin D Receptor in Osteoblasts and Osteocytes: MEDIATION BY Src, PHOSPHATIDYLINOSITOL 3-, AND JNK KINASES.
A. M. Vertino, C. M. Bula, J.-R. Chen, M. Almeida, L. Han, T. Bellido, S. Kousteni, A. W. Norman, and S. C. Manolagas (2005)
J. Biol. Chem. 280, 14130-14137
   Abstract »    Full Text »    PDF »
Extracellular Signal-Regulated Protein Kinase, But Not c-Jun N-Terminal Kinase, Is Activated by Type II Gonadotropin-Releasing Hormone Involved in the Inhibition of Ovarian Cancer Cell Proliferation.
K.-Y. Kim, K.-C. Choi, S.-H. Park, N. Auersperg, and P. C. K. Leung (2005)
J. Clin. Endocrinol. Metab. 90, 1670-1677
   Abstract »    Full Text »    PDF »
Bisphosphonates and Estrogens Inhibit Osteocyte Apoptosis via Distinct Molecular Mechanisms Downstream of Extracellular Signal-regulated Kinase Activation.
L. I. Plotkin, J. I. Aguirre, S. Kousteni, S. C. Manolagas, and T. Bellido (2005)
J. Biol. Chem. 280, 7317-7325
   Abstract »    Full Text »    PDF »
ERK Kinase Inhibition Stabilizes the Aryl Hydrocarbon Receptor: IMPLICATIONS FOR TRANSCRIPTIONAL ACTIVATION AND PROTEIN DEGRADATION.
S. Chen, T. Operana, J. Bonzo, N. Nguyen, and R. H. Tukey (2005)
J. Biol. Chem. 280, 4350-4359
   Abstract »    Full Text »    PDF »
Transient Versus Sustained Phosphorylation and Nuclear Accumulation of ERKs Underlie Anti-Versus Pro-apoptotic Effects of Estrogens.
J.-R. Chen, L. I. Plotkin, J. I. Aguirre, L. Han, R. L. Jilka, S. Kousteni, T. Bellido, and S. C. Manolagas (2005)
J. Biol. Chem. 280, 4632-4638
   Abstract »    Full Text »    PDF »
Induction of Ornithine Decarboxylase Activity Is a Necessary Step for Mitogen-Activated Protein Kinase Kinase-Induced Skin Tumorigenesis.
D. J. Feith, D. K. Bol, J. M. Carboni, M. J. Lynch, S. Sass-Kuhn, P. L. Shoop, and L. M. Shantz (2005)
Cancer Res. 65, 572-578
   Abstract »    Full Text »    PDF »
Ternary Complex Factor-Serum Response Factor Complex-Regulated Gene Activity Is Required for Cellular Proliferation and Inhibition of Apoptotic Cell Death.
E. R. Vickers, A. Kasza, I. A. Kurnaz, A. Seifert, L. A. H. Zeef, A. O'Donnell, A. Hayes, and A. D. Sharrocks (2004)
Mol. Cell. Biol. 24, 10340-10351
   Abstract »    Full Text »    PDF »
Vav Transformation Requires Activation of Multiple GTPases and Regulation of Gene Expression.
T. R. Palmby, K. Abe, A. E. Karnoub, and C. J. Der (2004)
Mol. Cancer Res. 2, 702-711
   Abstract »    Full Text »    PDF »
Inhibition of Extracellular-signal Regulated Kinases 1/2 Is Required for Apoptosis of Human Colon Cancer Cells In vitro by Sulindac Metabolites.
P. L. Rice, K. S. Beard, L. J. Driggers, and D. J. Ahnen (2004)
Cancer Res. 64, 8148-8151
   Abstract »    Full Text »    PDF »
Multicenter Phase II Study of the Oral MEK Inhibitor, CI-1040, in Patients With Advanced Non-Small-Cell Lung, Breast, Colon, and Pancreatic Cancer.
J. Rinehart, A. A. Adjei, P. M. LoRusso, D. Waterhouse, J. R. Hecht, R. B. Natale, O. Hamid, M. Varterasian, P. Asbury, E. P. Kaldjian, et al. (2004)
J. Clin. Oncol. 22, 4456-4462
   Abstract »    Full Text »    PDF »
Active Mutants of the Human p38{alpha} Mitogen-activated Protein Kinase.
R. Diskin, N. Askari, R. Capone, D. Engelberg, and O. Livnah (2004)
J. Biol. Chem. 279, 47040-47049
   Abstract »    Full Text »    PDF »
Changes in Androgen Receptor Nongenotropic Signaling Correlate with Transition of LNCaP Cells to Androgen Independence.
E. Unni, S. Sun, B. Nan, M. J. McPhaul, B. Cheskis, M. A. Mancini, and M. Marcelli (2004)
Cancer Res. 64, 7156-7168
   Abstract »    Full Text »    PDF »
Transformation Potential of Ras Isoforms Correlates with Activation of Phosphatidylinositol 3-Kinase but Not ERK.
W. Li, T. Zhu, and K.-L. Guan (2004)
J. Biol. Chem. 279, 37398-37406
   Abstract »    Full Text »    PDF »
Mek1 Alters Epidermal Growth and Differentiation.
F. A. Scholl, P. A. Dumesic, and P. A. Khavari (2004)
Cancer Res. 64, 6035-6040
   Abstract »    Full Text »    PDF »
Activation of Ras-Ral Pathway Attenuates p53-independent DNA Damage G2 Checkpoint.
L. S. Agapova, J. L. Volodina, P. M. Chumakov, and B. P. Kopnin (2004)
J. Biol. Chem. 279, 36382-36389
   Abstract »    Full Text »    PDF »
Reduction in Raf Kinase Inhibitor Protein Expression Is Associated with Increased Ras-Extracellular Signal-Regulated Kinase Signaling in Melanoma Cell Lines.
M. M. Schuierer, F. Bataille, S. Hagan, W. Kolch, and A.-K. Bosserhoff (2004)
Cancer Res. 64, 5186-5192
   Abstract »    Full Text »    PDF »
A Feedback Loop in the Polo-like Kinase Activation Pathway.
E. Erikson, T. A. J. Haystead, Y.-W. Qian, and J. L. Maller (2004)
J. Biol. Chem. 279, 32219-32224
   Abstract »    Full Text »    PDF »


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