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Science 9 December 1994:
Vol. 266. no. 5191, pp. 1719 - 1723
DOI: 10.1126/science.7992057
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Articles

Science, Vol 266, Issue 5191, 1719-1723
Copyright © 1994 by American Association for the Advancement of Science

articles

Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK

A Minden, A Lin, M McMahon, C Lange-Carter, B Derijard, RJ Davis, GL Johnson, and M Karin

Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla 92093-0636.

Growth factors activate mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs) and Jun kinases (JNKs). Although the signaling cascade from growth factor receptors to ERKs is relatively well understood, the pathway leading to JNK activation is more obscure. Activation of JNK by epidermal growth factor (EGF) or nerve growth factor (NGF) was dependent on H-Ras activation, whereas JNK activation by tumor necrosis factor alpha (TNF-alpha) was Ras-independent. Ras activates two protein kinases, Raf-1 and MEK (MAPK, or ERK, kinase) kinase (MEKK). Raf-1 contributes directly to ERK activation but not to JNK activation, whereas MEKK participated in JNK activation but caused ERK activation only after overexpression. These results demonstrate the existence of two distinct Ras-dependent MAPK cascades--one initiated by Raf-1 leading to ERK activation, and the other initiated by MEKK leading to JNK activation.


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M. Nomura, A. Kaji, Z. He, W.-Y. Ma, K.-i. Miyamoto, C. S. Yang, and Z. Dong (2001)
J. Biol. Chem. 276, 46624-46631
   Abstract »    Full Text »    PDF »
Cell Type-specific Inhibition of the ETS Transcription Factor ER81 by Mitogen-activated Protein Kinase-activated Protein Kinase 2.
R. Janknecht (2001)
J. Biol. Chem. 276, 41856-41861
   Abstract »    Full Text »    PDF »
Sustained Activation of Mitogen-Activated Protein Kinases and Activator Protein 1 by the Hepatitis B Virus X Protein in Mouse Hepatocytes In Vivo.
R. Nijhara, S. S. Jana, S. K. Goswami, A. Rana, S. S. Majumdar, V. Kumar, and D. P. Sarkar (2001)
J. Virol. 75, 10348-10358
   Abstract »    Full Text »    PDF »
Cellular stress response and apoptosis in cancer therapy.
I. Herr and K.-M. Debatin (2001)
Blood 98, 2603-2614
   Abstract »    Full Text »    PDF »
Hyperactivation of MAPK Induces Loss of ER{alpha} Expression in Breast Cancer Cells.
A. S. Oh, L. A. Lorant, J. N. Holloway, D. L. Miller, F. G. Kern, and D. El-Ashry (2001)
Mol. Endocrinol. 15, 1344-1359
   Abstract »    Full Text »    PDF »
Activation of the EGF receptor signaling pathway in airway epithelial cells exposed to Utah Valley PM.
W. Wu, J. M. Samet, A. J. Ghio, and R. B. Devlin (2001)
Am J Physiol Lung Cell Mol Physiol 281, L483-L489
   Abstract »    Full Text »    PDF »
Follicular Stage-Dependent Tumor Necrosis Factor {alpha}-Induced Hen Granulosa Cell Integrin Production and Survival in the Presence of Transforming Growth Factor {alpha} In Vitro.
J. Soboloff, H. Sasaki, and B.K. Tsang (2001)
Biol Reprod 65, 477-487
   Abstract »    Full Text »    PDF »
LDL-Activated p38 in Endothelial Cells Is Mediated by Ras.
Y. Zhu, H. Liao, N. Wang, K.-S. Ma, L. K. Verna, J. Y.-J. Shyy, S. Chien, and M. B. Stemerman (2001)
Arterioscler Thromb Vasc Biol 21, 1159-1164
   Abstract »    Full Text »    PDF »
Epidermal Growth Factor Regulation of Equine Glycoprotein Hormone {{alpha}} Subunit Expression in Trophoblast Cells.
T. M. Thway and M. W. Wolfe (2001)
Biol Reprod 65, 197-203
   Abstract »    Full Text »    PDF »
Insulin-Induced c-Jun N-Terminal Kinase Activation Is Negatively Regulated by Protein Kinase C {{delta}}.
K. Morino, H. Maegawa, T. Fujita, N. Takahara, K. Egawa, A. Kashiwagi, and R. Kikkawa (2001)
Endocrinology 142, 2669-2676
   Abstract »    Full Text »    PDF »
p38 MAP kinase negatively regulates cyclin D1 expression in airway smooth muscle cells.
K. Page, J. Li, and M. B. Hershenson (2001)
Am J Physiol Lung Cell Mol Physiol 280, L955-L964
   Abstract »    Full Text »    PDF »
Cdc42, but not RhoA, regulates cyclin D1 expression in bovine tracheal myocytes.
C. P. Bauerfeld, M. B. Hershenson, and K. Page (2001)
Am J Physiol Lung Cell Mol Physiol 280, L974-L982
   Abstract »    Full Text »    PDF »
Activation of c-Jun N-Terminal Kinase and Activator Protein 1 by Receptor Activator of Nuclear Factor kappa B.
Z. H. Lee, K. Kwack, K. K. Kim, S. H. Lee, and H.-H. Kim (2001)
Mol. Pharmacol. 58, 1536-1545
   Abstract »    Full Text »
Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions.
G. Pearson, F. Robinson, T. Beers Gibson, B.-e Xu, M. Karandikar, K. Berman, and M. H. Cobb (2001)
Endocr. Rev. 22, 153-183
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Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation.
J. M. Kyriakis and J. Avruch (2001)
Physiol Rev 81, 807-869
   Abstract »    Full Text »    PDF »
Regulation of gene expression by the small GTPase Rho through the ERK6 (p38{gamma}) MAP kinase pathway.
M. J. Marinissen, M. Chiariello, and J. S. Gutkind (2001)
Genes & Dev. 15, 535-553
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Regulation of the Urokinase-type Plasminogen Activator Receptor Gene in Different Grades of Human Glioma Cell Lines.
A. Bhattacharya, S. S. Lakka, S. Mohanam, D. Boyd, and J. S. Rao (2001)
Clin. Cancer Res. 7, 267-276
   Abstract »    Full Text »
K-ras Codon 12 Mutation Induces Higher Level of Resistance to Apoptosis and Predisposition to Anchorage-independent Growth Than Codon 13 Mutation or Proto-Oncogene Overexpression.
S. Guerrero, I. Casanova, L. Farré, A. Mazo, G. Capellà, and R. Mangues (2000)
Cancer Res. 60, 6750-6756
   Abstract »    Full Text »
MEKK1 Activation of Human Estrogen Receptor {alpha} and Stimulation of the Agonistic Activity of 4-Hydroxytamoxifen in Endometrial and Ovarian Cancer Cells.
H. Lee, F. Jiang, Q. Wang, S. V. Nicosia, J. Yang, B. Su, and W. Bai (2000)
Mol. Endocrinol. 14, 1882-1896
   Abstract »    Full Text »
Sequential Activation of ERK and Repression of JNK by Scatter Factor/Hepatocyte Growth Factor in Madin-Darby Canine Kidney Epithelial Cells.
R. Paumelle, D. Tulasne, C. Leroy, J. Coll, B. Vandenbunder, and V. Fafeur (2000)
Mol. Biol. Cell 11, 3751-3763
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Abl Interactor 1 Binds to Sos and Inhibits Epidermal Growth Factor- and v-Abl-Induced Activation of Extracellular Signal-Regulated Kinases.
P.-D. Fan and S. P. Goff (2000)
Mol. Cell. Biol. 20, 7591-7601
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Accumulation of RXR{alpha} During Activation of Cycling Human T Lymphocytes: Modulation of RXRE Transactivation Function by Mitogen-Activated Protein Kinase Pathways.
M. Ishaq, M. Fan, and V. Natarajan (2000)
J. Immunol. 165, 4217-4225
   Abstract »    Full Text »    PDF »
Growth Factor-Independent Proliferation of Erythroid Cells Infected with Friend Spleen Focus-Forming Virus Is Protein Kinase C Dependent but Does Not Require Ras-GTP.
K. W. Muszynski, D. Thompson, C. Hanson, R. Lyons, A. Spadaccini, and S. K. Ruscetti (2000)
J. Virol. 74, 8444-8451
   Abstract »    Full Text »


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